MedWorm.com provides a medical RSS filtering service. Over 6000 RSS medical sources are combined and output via different filters. This feed contains the latest items from the 'Cellular Microbiology' source. Mon, 06 Feb 2012 21:32:07 +0100 http://www.medworm.com/index.php?rid=5644306&cid=s_32061_77_f&fid=32061&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1462-5822.2012.01761.x SummaryLegionella pneumophila is a human pathogen causing severe pneumonia called Legionnaires' disease. Multiple Legionella effectors are type IV‐secreted into the host cell to establish a specific vesicular compartment for pathogen replication. Recently it has been reported that the Legionella effector SetA shares sequence similarity with glycosyltransferases and interferes with vesicular trafficking of host cells (Heidtman et al., 2009, Cell Microbiol 11: 230). Here we show that SetA possesses glycohydrolase and mono‐O‐glucosyltransferase activity by using UDP‐glucose as a donor substrate. Whereas the catalytic activity is located at the N terminus of SetA, the C terminus (amino acids 401‐644) is essential for guidance of SetA to vesicular compartments of host cells. EGFP‐Se... Cellular Microbiology journals http://www.medworm.com/rss/comments.php?id=5644306 Tue, 31 Jan 2012 20:40:43 +0100 5644306 http://www.medworm.com/index.php?rid=5644310&cid=s_32061_77_f&fid=32061&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1462-5822.2012.01757.x SummaryFor both pathogenic fungi and bacteria, extracellular vesicles have been shown to contain many microbial components associated with virulence, suggesting a role in pathogenesis. However, there are many unresolved issues regarding vesicle synthesis and stability, including the fact that vesicular packaging for extracellular factors involved in virulence must also have a mechanism for vesicle unloading. Consequently, we studied the kinetics of vesicle production and stability using [1‐14C] palmitic acid metabolic labeling and dynamic light scattering techniques. Cryptococcus neoformans vesicles were produced throughout all stages of fungal culture growth and they were stable once isolated. Density gradient analysis revealed that only a portion of the vesicle population carried crypt... Cellular Microbiology journals http://www.medworm.com/rss/comments.php?id=5644310 Tue, 31 Jan 2012 05:00:00 +0100 5644310 http://www.medworm.com/index.php?rid=5644309&cid=s_32061_77_f&fid=32061&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1462-5822.2012.01758.x SummaryThe nucleus, at the heart of the eukaryotic cell, hosts and protects the genetic material, governs gene expression and regulates the whole cell physiology, including cell division. A growing number of studies indicate that various animal and plant pathogenic bacteria can deliver factors to this central organelle to subvert host defenses by directly interfering with transcription, chromatin‐remodeling, RNA splicing or DNA replication and repair. Such bacterial molecules entering the nucleus, which we propose to term “nucleomodulins”, use diverse strategies to hijack nuclear processes by targeting host DNA or an array of nuclear proteins. In some cases, bacteria can even enter the nucleus. These bacterial “nuclear attacks” might have permanent genetic or long‐term epigenet... Cellular Microbiology journals http://www.medworm.com/rss/comments.php?id=5644309 Tue, 31 Jan 2012 05:00:00 +0100 5644309 http://www.medworm.com/index.php?rid=5644308&cid=s_32061_77_f&fid=32061&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1462-5822.2012.01760.x SummaryMycoplasma hyorhinis frequently contaminates cultured cells, with effects on synthetic and metabolic pathways. We demonstrated for the first time that contamination of cells by a strain of M. hyorhinis (NDMh) results in increased levels of calpastatin (the endogenous inhibitor of the ubiquitous Ca2+‐dependent protease calpain). We now show that the calpastatin upregulation by NDMh in neuroblastoma SH‐SY5Y cells resides in the NDMh lipoprotein fraction (LPP), via the NF‐κB transcription pathway. NF‐κB activation requires dissociation of the cytoplasmic NF‐κB/IκB complex followed by NF‐κB translocation to the nucleus. NDMh‐LPP induced translocation of the NF‐κB/RelA subunit to the nucleus and upregulated calpastatin. RelA translocation and calpastatin elevation w... Cellular Microbiology journals http://www.medworm.com/rss/comments.php?id=5644308 Tue, 31 Jan 2012 05:00:00 +0100 5644308 http://www.medworm.com/index.php?rid=5644307&cid=s_32061_77_f&fid=32061&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1462-5822.2012.01759.x This study is focused on the role of the influenza A virus matrix protein M1 in virus release. We found that a mutation of the proline residue at position 16 of the matrix protein induces inhibition of virus detachment from cells. Depletion of the M1‐binding protein RACK1 also impairs virus release and RACK1 binding requires the proline residue at position 16 of M1. The impaired M1‐RACK1 interaction does not affect the plasma membrane binding of M1; in contrast, RACK1 is recruited to detergent‐resistant membranes in a M1‐proline‐16‐dependent manner. The proline‐16 mutation in M1 and depletion of RACK1 impairs the pinching‐off of the budding virus particles. These findings reveal the active role of the viral matrix protein in the release of influenza A virus particles that i... Cellular Microbiology journals http://www.medworm.com/rss/comments.php?id=5644307 Tue, 31 Jan 2012 05:00:00 +0100 5644307 http://www.medworm.com/index.php?rid=5617504&cid=s_32061_77_f&fid=32061&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1462-5822.2012.01756.x SummaryProteins of the Leishmania HASPB family are only expressed in infective parasites (both extra‐ and intracellular stages) and, together with the peripheral membrane protein SHERP, are essential for parasite differentiation (metacyclogenesis) in the sand fly vector. HASPB is a “non‐classically” secreted protein, requiring N‐terminal acylation for trafficking to and exposure on the plasma membrane. Here, we use live cell imaging methods to further explore this pathway to the membrane and flagellum. Unlike HASPB trafficking in transfected mammalian cells, we find no evidence for a phosphorylation‐regulated recycling pathway in metacyclic parasites. Once at the plasma membrane, HASPB18‐GFP can undergo bidirectional movement within the inner leaflet of the membrane and on th... Cellular Microbiology journals http://www.medworm.com/rss/comments.php?id=5617504 Sun, 22 Jan 2012 02:11:11 +0100 5617504 http://www.medworm.com/index.php?rid=5604521&cid=s_32061_77_f&fid=32061&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1462-5822.2011.01732.x (Source: Cellular Microbiology) Cellular Microbiology journals http://www.medworm.com/rss/comments.php?id=5604521 Thu, 19 Jan 2012 02:52:51 +0100 5604521 http://www.medworm.com/index.php?rid=5604518&cid=s_32061_77_f&fid=32061&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1462-5822.2012.01754.x SummaryMycobacterium tuberculosis is an intracellular bacterium that can survive within macrophages. Such survival is potentially associated with Coronin‐1a (Coro1a). We investigated the mechanism by which Coro1a promotes the survival of M. tuberculosis in macrophages and found that autophagy was involved in the inhibition of mycobacterial survival in Coro1a knockdown (KD) macrophages. Fluorescence microscopy and immunoblot analyses revealed that LC3, a representative autophagic protein, was recruited to M. tuberculosis‐containing phagosomes in Coro1a KD macrophages. Thin‐section electron microscopy demonstrated that bacilli were surrounded by the multiple membrane structures in Coro1a KD macrophages. The proportion of LC3‐postive mycobacterial phagosomes colocalized with p62/SQSTM... Cellular Microbiology journals http://www.medworm.com/rss/comments.php?id=5604518 Thu, 19 Jan 2012 02:52:00 +0100 5604518 http://www.medworm.com/index.php?rid=5604519&cid=s_32061_77_f&fid=32061&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1462-5822.2012.01755.x SummaryESX‐5 is a mycobacterial type VII protein secretion system responsible for transport of numerous PE and PPE proteins. It is involved in the induction of host cell death and modulation of the cytokine response in vitro. In this work, we studied the effects of ESX‐5 in embryonic and adult zebrafish using Mycobacterium marinum. We found that ESX‐5‐deficient M. marinum was slightly attenuated in zebrafish embryos. Surprisingly, the same mutant showed highly increased virulence in adult zebrafish, characterized by increased bacterial loads and early onset of granuloma formation with rapid development of necrotic centres. This early onset of granuloma formation was accompanied by an increased expression of proinflammatory cytokines and tissue remodelling genes in zebrafish infecte... Cellular Microbiology journals http://www.medworm.com/rss/comments.php?id=5604519 Wed, 18 Jan 2012 05:00:00 +0100 5604519 http://www.medworm.com/index.php?rid=5594047&cid=s_32061_77_f&fid=32061&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1462-5822.2012.01747.x In this study, we analyzed the recruitment of the COG complex and GS15‐positive COG complex‐dependent (CCD) vesicles to Chlamydia trachomatis inclusion and their participation in chlamydial growth. Immunofluorescent analysis revealed that both GFP‐tagged and endogenous COG complex subunits associated with inclusions in a serovar‐independent manner by 8 h post infection and were maintained throughout the entire developmental cycle. Golgi v‐SNARE GS15 was associated with inclusions 24 h post infection, but was absent on the mid‐cycle (8 h) inclusions, indicating that this Golgi SNARE is directed to inclusions after COG complex recruitment. Silencing of COG8 and GS15 by siRNA significantly decreased infectious yield of chlamydiae. Further, membranous structures likely derived from... Cellular Microbiology journals http://www.medworm.com/rss/comments.php?id=5594047 Tue, 10 Jan 2012 05:00:00 +0100 5594047 http://www.medworm.com/index.php?rid=5594046&cid=s_32061_77_f&fid=32061&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1462-5822.2012.01748.x AbstractThe identification of a major class of innate immune receptors, termed Pattern Recognition Receptors (PRRs), has boosted research on innate pathogen recognition. The immune response to a specific pathogen is not restricted to the recognition by one type of PRR or activation of a single cell type, but instead comprises complex collaborations between different receptors, cells, and signal mediators. Here we will discuss the crosstalk between PRRs involved in fungal recognition, focusing on the molecular interactions occurring at the plasma membrane. (Source: Cellular Microbiology) Cellular Microbiology journals http://www.medworm.com/rss/comments.php?id=5594046 Tue, 10 Jan 2012 05:00:00 +0100 5594046 http://www.medworm.com/index.php?rid=5594045&cid=s_32061_77_f&fid=32061&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1462-5822.2012.01749.x SummaryThe bacterial pathogen Pseudomonas syringae pv tomato DC3000 suppresses plant innate immunity with effector proteins injected by a type III secretion system (T3SS). The cysteine protease effector HopN1, which reduces the ability of DC3000 to elicit programmed cell death in nonhost tobacco, was found to also suppress the production of defense‐associated reactive oxygen species (ROS) and callose when delivered by Pseudomonas fluorescens heterologously expressing a P. syringae T3SS. Purified His6‐tagged HopN1 was used to identify tomato PsbQ, a member of the oxygen evolving complex of Photosystem II (PSII), as an interacting protein. HopN1 localized to chloroplasts and both degraded PsbQ and inhibited PSII activity in chloroplast preparations, whereas a HopN1D299A non‐catalytic m... Cellular Microbiology journals http://www.medworm.com/rss/comments.php?id=5594045 Tue, 10 Jan 2012 05:00:00 +0100 5594045 http://www.medworm.com/index.php?rid=5594044&cid=s_32061_77_f&fid=32061&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1462-5822.2012.01750.x (Source: Cellular Microbiology) Cellular Microbiology journals http://www.medworm.com/rss/comments.php?id=5594044 Tue, 10 Jan 2012 05:00:00 +0100 5594044 http://www.medworm.com/index.php?rid=5594043&cid=s_32061_77_f&fid=32061&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1462-5822.2012.01751.x AbstractAdapted filamentous pathogens such as the oomycetes Hyaloperonospora arabidopsidis (Hpa) and Phytophthora infestans (Pi) project specialized hyphae, the haustoria, inside living host cells for the suppression of host defense and acquisition of nutrients. Accommodation of haustoria requires reorganization of the host cell and the biogenesis of a novel host cell membrane, the extrahaustorial membrane (EHM), which envelops the haustorium separating the host cell from the pathogen. Here, we applied live‐cell imaging of fluorescent‐tagged proteins labeling a variety of membrane compartments and investigated the subcellular changes associated with accommodating oomycete haustoria in Arabidopsis and N. benthamiana. Plasma membrane‐resident proteins differentially localized to the EH... Cellular Microbiology journals http://www.medworm.com/rss/comments.php?id=5594043 Tue, 10 Jan 2012 05:00:00 +0100 5594043 http://www.medworm.com/index.php?rid=5594042&cid=s_32061_77_f&fid=32061&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1462-5822.2012.01752.x In this study, we determined the impact of the collagen fibers architecture on the invasive process of the enteric parasite Entamoeba histolytica. The behavior of E. histolytica wild type and silenced for the cysteine protease A5 (CP‐A5) were compared on a three‐dimensional collagen matrix and within human colon fragments for fibrillar collagen cleavage and migration. The interstitial collagen fibers within the connective tissue of the human colon, visualized by multiphoton and second harmonic generation signals imaging, presented a dense scaffold at the sub epithelial level and a loose meshwork within the chorion. To penetrate the tissue, E. histolytica migrated on the dense scaffold that remained intact, reached the crypt of Lieberkhün, migrated along and then disorganized the loose... Cellular Microbiology journals http://www.medworm.com/rss/comments.php?id=5594042 Tue, 10 Jan 2012 05:00:00 +0100 5594042 http://www.medworm.com/index.php?rid=5594041&cid=s_32061_77_f&fid=32061&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1462-5822.2012.01753.x SummaryPseudomonas aeruginosa (PA) forms biofilms in lungs of cystic fibrosis CF) patients, a process regulated by quorum sensing molecules including N‐(3‐oxododecanoyl)‐L‐homoserine lactone, C12. C12 (10‐100 µM) rapidly triggered events commonly associated with the intrinsic apoptotic pathway in JME (CF ?F508CFTR, nasal surface) epithelial cells: depolarization of mitochondrial (mito) membrane potential (?ψmito) and release of cytochrome C (cytoC) from mitos into cytosol and activation of caspases 3/7, 8 and 9. C12 also had novel effects on the endoplasmic reticulum (release of both Ca2+ and ER‐targeted GFP and oxidized contents into the cytosol). Effects began within 5 minutes and were complete in 1‐2 hrs. C12 caused similar activation of caspases and release of cytoC fro... Cellular Microbiology journals http://www.medworm.com/rss/comments.php?id=5594041 Sun, 01 Jan 2012 05:00:00 +0100 5594041 http://www.medworm.com/index.php?rid=5556988&cid=s_32061_77_f&fid=32061&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1462-5822.2011.01746.x SummaryStreptococcus pneumoniae is both a frequent colonizer of the upper respiratory tract and a leading cause of life‐threatening infections such as pneumonia, meningitis, and sepsis. The innate immune system is critical for the control of colonization and for defence during invasive disease. Initially, pneumococci are recognized by different sensors of the innate immune system called pattern recognition receptors (PRRs), which control most if not all subsequent host defense pathways. These PRRs include the transmembrane Toll‐like receptors (TLRs) as well as the cytosolic NOD‐like receptors (NLRs) and DNA sensors. Recognition of S. pneumoniae by members of these PRR families regulates the production of inflammatory mediators that orchestrate the following immune response of infecte... Cellular Microbiology journals http://www.medworm.com/rss/comments.php?id=5556988 Sun, 01 Jan 2012 05:00:00 +0100 5556988 http://www.medworm.com/index.php?rid=5556989&cid=s_32061_77_f&fid=32061&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1462-5822.2011.01745.x SummaryNutrient sensing and the capacity to respond to starvation is tightly regulated as a means of cell survival. Among the features of the starvation response are induction of both translational repression and autophagy. Despite the fact that intracellular parasite like Toxoplasma gondii within a host cell predicted to be nutrient rich, they encode genes involved both in translational repression and autophagy. We therefore examined the consequence of starvation, a classic trigger of autophagy, on intracellular parasites. As expected, starvation results in the activation of the translational repression system as evidenced by elevation of phosphorylated TgIF2α (TgIF2α‐P). Surprisingly, we also observe a rapid and selective fragmentation of the single parasite mitochondrion that leads ... Cellular Microbiology journals http://www.medworm.com/rss/comments.php?id=5556989 Fri, 30 Dec 2011 05:00:00 +0100 5556989 http://www.medworm.com/index.php?rid=5657238&cid=s_32061_77_f&fid=32061&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1462-5822.2011.01743.x SummaryPorphyromonas gingivalis, a host‐adapted opportunistic pathogen, produces a serine phosphatase, SerB, known to affect virulence, invasion and persistence within the host cell. SerB induces actin filament rearrangement in epithelial cells, but the mechanistic basis of this is not fully understood. Here we investigated the effects of SerB on the actin depolymerizing host protein cofilin. P. gingivalis infection resulted in the dephosphorylation of cofilin in gingival epithelial cells. In contrast, a SerB‐deficient mutant of P. gingivalis was unable to cause cofilin dephosphorylation. The involvement of cofilin in P. gingivalis invasion was determined by quantitative image analysis of epithelial cells in which cofilin had been knocked down or knocked in with various cofilin c... Cellular Microbiology journals http://www.medworm.com/rss/comments.php?id=5657238 Thu, 29 Dec 2011 05:00:00 +0100 5657238 http://www.medworm.com/index.php?rid=5556992&cid=s_32061_77_f&fid=32061&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1462-5822.2011.01742.x SUMMARYIntracellular cholesterol amounts, distribution, and traffic are tightly regulated to maintain the healthy eukaryotic cell function. However, how intracellular pathogens that require cholesterol, interact with the host cholesterol homeostasis and traffic is not well understood. Anaplasma phagocytophilum is an obligatory intracellular and cholesterol‐robbing bacterium, which causes human granulocytic anaplasmosis. Here we found that a subset of cholesterol‐binding membrane protein, Niemann–Pick type C1 (NPC1)‐bearing vesicles devoid of lysosomal markers were upregulated in HL‐60 cells infected with A. phagocytophilum, and trafficked to live bacterial inclusions. The NPC1 localization to A. phagocytophilum inclusions was abolished by low‐density lipoprotein (LDL)‐derived... Cellular Microbiology journals http://www.medworm.com/rss/comments.php?id=5556992 Thu, 29 Dec 2011 05:00:00 +0100 5556992 http://www.medworm.com/index.php?rid=5556991&cid=s_32061_77_f&fid=32061&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1462-5822.2011.01743.x SUMMARYPorphyromonas gingivalis a host‐adapted opportunistic pathogen produces a serine phosphatase, SerB, known to affect virulence, invasion and persistence within the host cell. SerB induces actin filament rearrangement in epithelial cells, but the mechanistic basis of this is not fully understood. Here we investigated the effects of SerB on the actin depolymerizing host protein cofilin. P. gingivalis infection resulted in the dephosphorylation of cofilin in gingival epithelial cells. In contrast, a SerB deficient mutant of P. gingivalis was unable to cause cofilin dephosphorylation. The involvement of cofilin in P. gingivalis invasion was determined by quantitative image analysis of epithelial cells in which cofilin had been knocked‐down or knocked‐in with various cofilin constru... Cellular Microbiology journals http://www.medworm.com/rss/comments.php?id=5556991 Thu, 29 Dec 2011 05:00:00 +0100 5556991 http://www.medworm.com/index.php?rid=5556990&cid=s_32061_77_f&fid=32061&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1462-5822.2011.01744.x SUMMARYBoth pathogenic and commensal strains of Escherichia coli colonize the human intestinal tract. Pathogenic strains differ only in the expression of virulence factors, many of which comprise a type III secretion system (TTSS). Little is known regarding the effect of E. coli on the intestinal epithelial response to the secretagogues that drive ion secretion, despite its importance in causing clinically significant diarrhea. Using Ussing chambers to measure electrogenic ion transport of T84 intestinal epithelial cell monolayers, we found that all strains of E. coli tested (pathogenic, commensal, probiotic and lab strain) significantly reduced cAMP‐dependent ion secretion after 4‐8 hr exposure. Enteropathogenic E. coli (EPEC) mutants lacking a functional TTSS caused similar hyposecre... Cellular Microbiology journals http://www.medworm.com/rss/comments.php?id=5556990 Thu, 29 Dec 2011 05:00:00 +0100 5556990 http://www.medworm.com/index.php?rid=5534282&cid=s_32061_77_f&fid=32061&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1462-5822.2011.01741.x ABSTRACTThe spleen is a complex organ that is perfectly adapted to selectively filtering and destroying senescent red blood cells (RBCs), infectious microorganisms and Plasmodium‐parasitized RBCs (pRBCs). Infection by malaria is the most common cause of spleen rupture and splenomegaly, albeit variably, a landmark of malaria infection. Here, the role of the spleen in malaria is reviewed with special emphasis in lessons learned from human infections and mouse models. (Source: Cellular Microbiology) Cellular Microbiology journals http://www.medworm.com/rss/comments.php?id=5534282 Fri, 23 Dec 2011 15:09:41 +0100 5534282 http://www.medworm.com/index.php?rid=5617509&cid=s_32061_77_f&fid=32061&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1462-5822.2011.01740.x SummaryThe reactivation of latent Epstein–Barr virus (EBV) to lytic replication is important in pathogenesis and requires virus–host cellular interactions. However, the mechanism underlying the reactivation of EBV is not yet fully understood. In the present study, herpes simplex virus type 1 (HSV‐1) was shown to induce the reactivation of latent EBV by triggering BZLF1 expression. The BZLF1 promoter (Zp) was not activated by HSV‐1 essential glycoprotein‐induced membrane fusion. Nevertheless, Zp was activated within 6 h post HSV‐1 infection in virus entry‐dependent and replication‐independent manners. Using a panel of Zp deletion mutants, HSV‐1 was shown to promote Zp through a cyclic adenosine monophosphate (cAMP) response element (CRE) located in ZII. The phosphorylate... Cellular Microbiology journals http://www.medworm.com/rss/comments.php?id=5617509 Thu, 22 Dec 2011 05:00:00 +0100 5617509 http://www.medworm.com/index.php?rid=5534284&cid=s_32061_77_f&fid=32061&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1462-5822.2011.01733.x In this study, we show that SpvC can be delivered into the host cell cytoplasm by both SPI‐1 and SPI‐2 T3SSs. Dephosphorylation of the extracellular signal‐regulated protein kinases (ERK) was detected in an SPI‐1 T3SS‐dependent manner 2 hours post infection. Using a mouse model for Salmonella enterocolitis, which was treated with streptomycin prior to infection, we observed that mice infected with Salmonellaenterica serovar Typhimurium strains lacking the spvC gene showed pronounced colitis when compared to mice infected with the wild‐type strain 1 day after infection. The effect of SpvC on the development of colitis was characterized by reduced mRNA levels of the proinflammatory cytokines and chemokines, and reduced inflammation with less infiltration of neutrophils. Furthermo... Cellular Microbiology journals http://www.medworm.com/rss/comments.php?id=5534284 Thu, 22 Dec 2011 05:00:00 +0100 5534284 http://www.medworm.com/index.php?rid=5534283&cid=s_32061_77_f&fid=32061&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1462-5822.2011.01740.x SummaryThe reactivation of latent Epstein‐Barr virus (EBV) to lytic replication is important in pathogenesis and requires virus‐host cellular interactions. However, the mechanism underlying the reactivation of EBV is not yet fully understood. In the present study, Herpes Simplex Virus Type 1 (HSV‐1) was shown to induce the reactivation of latent EBV by triggering BZLF1 expression. The BZLF1 promoter (Zp) was not activated by HSV‐1 essential glycoprotein‐induced membrane fusion. Nevertheless, Zp was activated within 6 h post‐HSV‐1 infection in virus‐entry‐dependent and replication‐independent manners. Using a panel of Zp deletion mutants, HSV‐1 was shown to promote Zp through a cyclic adenosine monophosphate (cAMP)‐response element (CRE) located in ZII. The phosphory... Cellular Microbiology journals http://www.medworm.com/rss/comments.php?id=5534283 Thu, 22 Dec 2011 05:00:00 +0100 5534283 http://www.medworm.com/index.php?rid=5520944&cid=s_32061_77_f&fid=32061&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1462-5822.2011.01739.x SUMMARYRickettsiae are obligate intracellular pathogens that are transmitted to humans by arthropod vectors and cause diseases such as spotted fever and typhus. Although rickettsiae require the host cell actin cytoskeleton for invasion, the cytoskeletal proteins that mediate this process have not been completely described. To identify the host factors important during cell invasion by Rickettsia parkeri, a member of the spotted fever group (SFG), we performed an RNAi screen targeting 105 proteins in Drosophila melanogaster S2R+ cells. The screen identified 21 core proteins important for invasion, including the GTPases Rac1 and Rac2, the WAVE nucleation promoting factor complex and the Arp2/3 complex. In mammalian cells, including endothelial cells, the natural targets of R. parkeri, the Ar... Cellular Microbiology journals http://www.medworm.com/rss/comments.php?id=5520944 Tue, 20 Dec 2011 14:11:29 +0100 5520944 http://www.medworm.com/index.php?rid=5604520&cid=s_32061_77_f&fid=32061&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1462-5822.2011.01738.x SummaryThe signals that guide neutrophils to sites of tissue injury or infection remain elusive. H2O2 has been implicated in neutrophil sensing of tissue injury and transformed cells; however, its role in neutrophil recruitment to infection has not been explored. Here, using a pharmacological inhibitor of NADPH oxidases, diphenyleneiodonium (DPI), and genetic depletion of an epithelial‐specific NADPH oxidase, we show that H2O2 is not required for neutrophil detection of localized infection with the Gram‐negative bacterium Pseudomonas aeruginosa. In contrast, PI3K signalling is required for neutrophil responses to both wounding and infection. In vivo imaging using a H2O2 probe detects dynamic H2O2 generation at wounds but not at infected tissue. Moreover, DPI no longer inhibits neutroph... Cellular Microbiology journals http://www.medworm.com/rss/comments.php?id=5604520 Tue, 20 Dec 2011 05:00:00 +0100 5604520 http://www.medworm.com/index.php?rid=5520945&cid=s_32061_77_f&fid=32061&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1462-5822.2011.01738.x SummaryThe signals that guide neutrophils to sites of tissue injury or infection remain elusive. H2O2 has been implicated in neutrophil sensing of tissue injury and transformed cell, however its role in neutrophil recruitment to infection has not been explored. Here, using a pharmacological inhibitor of NADPH oxidases, diphenyleneiodonium (DPI), and genetic depletion of an epithelial specific NADPH oxidase, we show that H2O2 is not required for neutrophil detection of localized infection with the Gram‐negative bacterium Pseudomonas aeruginosa. In contrast, PI3K signaling is required for neutrophil responses to both wounding and infection. In vivo imaging using a H2O2 probe detects dynamic H2O2 generation at wounds but not at infected tissue. Moreover, DPI no longer inhibits neutrophil wo... Cellular Microbiology journals http://www.medworm.com/rss/comments.php?id=5520945 Tue, 20 Dec 2011 05:00:00 +0100 5520945 http://www.medworm.com/index.php?rid=5513000&cid=s_32061_77_f&fid=32061&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1462-5822.2011.01728.x (Source: Cellular Microbiology) Cellular Microbiology journals http://www.medworm.com/rss/comments.php?id=5513000 Sat, 17 Dec 2011 14:43:29 +0100 5513000 http://www.medworm.com/index.php?rid=5512999&cid=s_32061_77_f&fid=32061&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1462-5822.2011.01725.x (Source: Cellular Microbiology) Cellular Microbiology journals http://www.medworm.com/rss/comments.php?id=5512999 Sat, 17 Dec 2011 14:43:28 +0100 5512999 http://www.medworm.com/index.php?rid=5512998&cid=s_32061_77_f&fid=32061&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1462-5822.2011.01731.x (Source: Cellular Microbiology) Cellular Microbiology journals http://www.medworm.com/rss/comments.php?id=5512998 Sat, 17 Dec 2011 14:43:08 +0100 5512998 http://www.medworm.com/index.php?rid=5657237&cid=s_32061_77_f&fid=32061&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1462-5822.2011.01736.x SummaryLegume plants are able to engage in root nodule symbiosis with nitrogen‐fixing soil bacteria, collectively called rhizobia. This mutualistic association is highly specific, such that each rhizobial species/strain interacts with only a specific group of legumes, and vice versa. Symbiosis specificity can occur at multiple phases of the interaction, ranging from initial bacterial attachment and infection to late nodule development associated with nitrogen fixation. Genetic control of symbiosis specificity is complex, involving fine‐tuned signal communication between the symbiotic partners. Here we review our current understanding of the mechanisms used by the host and bacteria to choose their symbiotic partners, with a special focus on the role that the host immunity plays in contr... Cellular Microbiology journals http://www.medworm.com/rss/comments.php?id=5657237 Tue, 13 Dec 2011 05:00:00 +0100 5657237 http://www.medworm.com/index.php?rid=5501770&cid=s_32061_77_f&fid=32061&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1462-5822.2011.01736.x SummaryLegume plants are able to engage in root nodule symbiosis with nitrogen‐fixing soil bacteria, collectively called rhizobia. This mutualistic association is highly specific, such that each rhizobial species/strain interacts with only a specific group of legumes, and vice versa. Symbiosis specificity can occur at multiple phases of the interaction, ranging from initial bacterial attachment and infection to late nodule development associated with nitrogen fixation. Genetic control of symbiosis specificity is complex, involving fine‐tuned signal communication between the symbiotic partners. Here we review our current understanding of the mechanisms used by the host and bacteria to choose their symbiotic partners, with a special focus on the role that the host immunity plays in contr... Cellular Microbiology journals http://www.medworm.com/rss/comments.php?id=5501770 Tue, 13 Dec 2011 05:00:00 +0100 5501770 http://www.medworm.com/index.php?rid=5493030&cid=s_32061_77_f&fid=32061&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1462-5822.2011.01734.x SUMMARYFor those stricken with malaria, the classic clinical symptoms are caused by the parasite's cyclic infection of red blood cells. However, this erythrocytic phase of the parasite's life cycle initiates from an asymptomatic pre‐erythrocytic phase: the injection of sporozoites via the bite of a parasite‐carrying Anopheline mosquito, and the ensuing infection of the liver. With the increased capabilities of studying liver stages in mice, much progress has been made elucidating the cellular and molecular basis of the parasite's progression through this bottleneck of its lifecycle. Here we review relevant findings on how sporozoites prepare for infection of the liver and factors crucial to liver stage development as well as key host/parasite interactions. (Source: Cellular Microbiolog... Cellular Microbiology journals http://www.medworm.com/rss/comments.php?id=5493030 Fri, 09 Dec 2011 05:00:00 +0100 5493030 http://www.medworm.com/index.php?rid=5501769&cid=s_32061_77_f&fid=32061&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1462-5822.2011.01737.x AbstractDuring intracellular parasitic infections, pathogens and host cells take part in a complex web of events that are crucial for the outcome of the infection. Modulation of host cell apoptosis by pathogens attracted the attention of scientists during the last decade. Apoptosis is an efficient mechanism used by the host to control infection and limit pathogen multiplication and dissemination. In order to ensure completion of their complex life cycles and to guarantee transmission between different hosts, intracellular parasites have developed mechanisms to block apoptosis and sustain the viability of their host cells. Here, we review how some of the most prominent intracellular protozoan parasites modulate the main mammalian apoptotic pathways by emphasizing the advances from the last ... Cellular Microbiology journals http://www.medworm.com/rss/comments.php?id=5501769 Thu, 01 Dec 2011 05:00:00 +0100 5501769 http://www.medworm.com/index.php?rid=5493029&cid=s_32061_77_f&fid=32061&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1462-5822.2011.01735.x AbstractIn previous studies we showed that the replication of Cryptococcus neoformans in the lung environment is controlled by the glucosylceramide (GlcCer) synthase gene (GCS1), which synthesizes the membrane sphingolipid GlcCer from the C9‐methyl ceramide. Here, we studied the effect of the mutation of the sphingolipid C9 methyltransferase gene (SMT1), which adds a methyl group to position 9 of the sphingosine backbone of ceramide. The C. neoformansΔsmt1 mutant does not make C9‐methyl ceramide and, thus, any methylated GlcCer. However, it accumulates de‐methylated ceramide and de‐methylated GlcCer. The Δsmt1 mutant loses more than 80% of its virulence compared to the wild‐type and the reconstituted strain. Interestingly, growth of C. neoformansΔsmt1 in the lung was decreased... Cellular Microbiology journals http://www.medworm.com/rss/comments.php?id=5493029 Thu, 01 Dec 2011 05:00:00 +0100 5493029 http://www.medworm.com/index.php?rid=5465784&cid=s_32061_77_f&fid=32061&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1462-5822.2011.01730.x SUMMARYAnimal African trypanosomiasis is a major constraint to livestock productivity and has an important impact on millions of people in developing African countries. This parasitic disease, caused mainly by Trypanosoma congolense, results in severe anaemia leading to animal death. In order to characterise potential targets for an anti‐disease vaccine, we investigated a multigenic trans‐sialidase family (TcoTS) in T. congolense. Sialidase and trans‐sialidase activities were quantified for the first time, as well as the tightly regulated TcoTS expression pattern throughout the life cycle. Active enzymes were expressed in bloodstream form parasites and released into the blood during infection. Using genetic tools, we demonstrated a significant correlation between TcoTS silencing and ... Cellular Microbiology journals http://www.medworm.com/rss/comments.php?id=5465784 Thu, 01 Dec 2011 05:00:00 +0100 5465784 http://www.medworm.com/index.php?rid=5465785&cid=s_32061_77_f&fid=32061&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1462-5822.2011.01729.x AbstractLipoic acid is an essential cofactor for enzymes that participate in key metabolic pathways in most organisms. While in mammalian cells lipoylated proteins reside exclusively in the mitochondria, apicomplexan parasites of the genus Plasmodium harbor two independent lipoylation pathways in the mitochondrion and the apicoplast, a second organelle of endosymbiotic origin. Protein lipoylation in the apicoplast relies on de novo lipoic acid synthesis while lipoylation of proteins in the mitochondrion depends on scavenging of lipoic acid from the host cell.Here, we analyze the impact of lipoic acid scavenging on the development of Plasmodium berghei liver stage parasites. Treatment of P. berghei‐infected HepG2 cells with the lipoic acid analog 8‐bromo‐octanoic acid (8‐BOA) abolis... Cellular Microbiology journals http://www.medworm.com/rss/comments.php?id=5465785 Wed, 30 Nov 2011 05:00:00 +0100 5465785 http://www.medworm.com/index.php?rid=5437729&cid=s_32061_77_f&fid=32061&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1462-5822.2011.01727.x In this study, we postulate that PCN causes and exacerbates GCH and mucus hypersecretion in bronchiectatic airways chronically infected by PA by inactivating FoxA2. We demonstrate that PCN represses the expression of FoxA2 in mouse airways and in bronchial epithelial cells cultured at an air‐liquid interface or conventionally, resulting in GCH, increased MUC5B mucin gene expression and mucus hypersecretion. Immunohistochemical and inhibitor studies indicate that PCN upregulates the expression of Stat6 and EGFR, both of which in turn repress the expression of FoxA2. These studies demonstrate that PCN induces GCH and mucus hypersecretion by inactivating FoxA2. (Source: Cellular Microbiology) Cellular Microbiology journals http://www.medworm.com/rss/comments.php?id=5437729 Wed, 23 Nov 2011 14:29:39 +0100 5437729 http://www.medworm.com/index.php?rid=5437730&cid=s_32061_77_f&fid=32061&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1462-5822.2011.01726.x SummaryThe subcellular localization and function of variant subtelomeric multigene families in Plasmodium vivax remain vastly unknown. Among them, the vir superfamily is putatively involved in antigenic variation and in mediating adherence to endothelial receptors. In the absence of a continuous in vitro culture system for P. vivax, we have generated P. falciparum transgenic lines expressing VIR proteins to infer location and function. We chose three proteins pertaining to subfamilies A (VIR17), C (VIR14) and D (VIR10), with domains and secondary structures that predictably traffic these proteins to different subcellular compartments. Here, we showed that VIR17 remained inside the parasite and around merozoites, whereas VIR14 and VIR10 were exported to the membrane of infected red blood ce... Cellular Microbiology journals http://www.medworm.com/rss/comments.php?id=5437730 Mon, 21 Nov 2011 05:00:00 +0100 5437730 http://www.medworm.com/index.php?rid=5418550&cid=s_32061_77_f&fid=32061&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1462-5822.2010.01723.x (Source: Cellular Microbiology) Cellular Microbiology journals http://www.medworm.com/rss/comments.php?id=5418550 Fri, 18 Nov 2011 05:08:25 +0100 5418550 http://www.medworm.com/index.php?rid=5397542&cid=s_32061_77_f&fid=32061&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1462-5822.2011.01722.x SummaryNadA (Neisseria meningitidisadhesin A), a meningococcal surface protein, mediates adhesion to and invasion of human cells, an activity in which host membrane proteins have been implicated. While investigating these host factors in human epithelial cells by affinity chromatography, we discovered an unanticipated interaction of NadA with heat shock protein (Hsp) 90, a molecular chaperone. The specific in vitro interaction of recombinant soluble NadA and Hsp90 was confirmed by co‐immunoprecipitations, dot and far‐Western blot. Intriguingly, ADP, but not ATP, was required for this association, and the Hsp90 inhibitor 17‐AAG promoted complex formation. Hsp90 binding to an Escherichia coli strain used as carrier to express surface exposed NadA confirmed these results in live bacteri... Cellular Microbiology journals http://www.medworm.com/rss/comments.php?id=5397542 Tue, 08 Nov 2011 05:00:00 +0100 5397542 http://www.medworm.com/index.php?rid=5376561&cid=s_32061_77_f&fid=32061&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1462-5822.2011.01720.x AbstractViruses are the most abundant and diverse pathogens challenging the host immune system, and as such are a severe threat to human health. To this end, viruses have evolved multiple strategies to evade and subvert the host immune response. Host‐pathogen interactions are usually initiated via recognition of pathogen associated molecular patterns (PAMPs) by host sensors known as pathogen recognition receptors (PRRs), which include, Toll‐like receptors (TLRs), RIG‐I‐like receptors (RLRs), NOD‐like receptors (NLRs) and DNA receptors. Effective sensing of PAMPs rapidly triggers host immune responses, via activation of complex signaling pathways that culminates in the induction of inflammatory responses and the eradication of pathogens. Activation of the nuclear factor‐κB (NF�... Cellular Microbiology journals http://www.medworm.com/rss/comments.php?id=5376561 Thu, 03 Nov 2011 04:00:00 +0100 5376561 http://www.medworm.com/index.php?rid=5437731&cid=s_32061_77_f&fid=32061&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1462-5822.2011.01719.x SummaryBacterial infections cause substantial mortality and burden of disease globally. Induction of a strong innate inflammatory response is the first common host mechanism required for elimination of the invading pathogens. The host transcription factor, nuclear factor kappa B (NF‐κB) is essential for immune activation. Conversely, bacterial pathogens have evolved strategies to interfere directly with host cell signalling by regulating or mimicking host proteins. Given the key role of NF‐κB in the host inflammatory response, bacteria have expectedly developed virulence effectors interfering with NF‐κB signalling pathways. In this review, we explore the bacterial mechanisms utilized to prevent effective NF‐κB signalling, which in turn usurp the host inflammatory response. (Sou... Cellular Microbiology journals http://www.medworm.com/rss/comments.php?id=5437731 Tue, 01 Nov 2011 04:00:00 +0100 5437731 http://www.medworm.com/index.php?rid=5397541&cid=s_32061_77_f&fid=32061&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1462-5822.2011.01724.x SummaryStreptolysin O (SLO) is a cholesterol dependent cytolysin (CDC) from Streptococcus pyogenes. SLO induces diverse types of Ca2+ signalling in host cells which play a key role in membrane repair and cell fate determination. The mechanisms behind SLO‐induced Ca2+ signalling remain poorly understood. Here, we show that in NCI‐H441 cells, wild type SLO as well as non‐pore forming mutant induces long‐lasting intracellular Ca2+ oscillations via IP3 mediated depletion of intracellular stores and activation of store dependent Ca2+ (SOC) entry. SLO‐induced activation of SOC entry was confirmed by Ca2+ add‐back experiments, pharmacologically and by overexpression as well as silencing of STIM1 and Orai1 expression.SLO also activated SOC entry in primary cultivated alveolar type II (... Cellular Microbiology journals http://www.medworm.com/rss/comments.php?id=5397541 Tue, 01 Nov 2011 04:00:00 +0100 5397541 http://www.medworm.com/index.php?rid=5376563&cid=s_32061_77_f&fid=32061&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1462-5822.2011.01718.x This study establishes that bacterial effectors utilize a normal host cell mechanism to locate the plasma membrane where they can then access their intracellular targets. (Source: Cellular Microbiology) Cellular Microbiology journals http://www.medworm.com/rss/comments.php?id=5376563 Tue, 01 Nov 2011 04:00:00 +0100 5376563 http://www.medworm.com/index.php?rid=5376562&cid=s_32061_77_f&fid=32061&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1462-5822.2011.01719.x AbstractBacterial infections cause substantial mortality and burden of disease globally. Induction of a strong innate inflammatory response is the first common host mechanism required for elimination of the invading pathogens. The host transcription factor, nuclear factor kappa B (NF‐κB) is essential for immune activation. Conversely, bacterial pathogens have evolved strategies to interfere directly with host cell signaling by regulating or mimicking host proteins. Given the key role of NF‐κB in the host inflammatory response, bacteria have expectedly developed virulence effectors interfering with NF‐κB signaling pathways. In this review, we explore the bacterial mechanisms utilized to prevent effective NF‐κB signaling, which in turn usurp the host inflammatory response. (Sourc... Cellular Microbiology journals http://www.medworm.com/rss/comments.php?id=5376562 Tue, 01 Nov 2011 04:00:00 +0100 5376562 http://www.medworm.com/index.php?rid=5376560&cid=s_32061_77_f&fid=32061&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1462-5822.2011.01721.x In this study for the first time, Mtb isogenic mutants missing selected PE_PGRSs were used to investigate their role in the pathogenesis of tuberculosis (TB). We demonstrate that the MtbΔPE_PGRS30 mutant was impaired in its ability to colonize lung tissue and to cause tissue damage, specifically during the chronic steps of infection. Inactivation of PE_PGRS30 resulted in an attenuated phenotype in murine and human macrophages due to the inability of the Mtb mutant to inhibit phagosome‐lysosome fusion. Using a series of functional deletion mutants of PE_PGRS30 to complement Mtb ΔPE_PGRS30, we show that the unique C‐terminal domain of the protein is not required for the full virulence. Interestingly, when M. smegmatis recombinant strain expressing PE_PGRS30 was used to infect macrophag... Cellular Microbiology journals http://www.medworm.com/rss/comments.php?id=5376560 Tue, 01 Nov 2011 04:00:00 +0100 5376560 http://www.medworm.com/index.php?rid=5437732&cid=s_32061_77_f&fid=32061&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1462-5822.2011.01717.x SummarySome pathogens are able to establish themselves within the host because they have evolved mechanisms to disrupt host innate immunity. For example, a number of pathogens secrete preformed effector proteins via type III secretion apparatuses that influence innate immune or apoptotic signalling pathways. One group of effector proteins that usurp innate immune signalling is the YopJ‐like family of bacterial effector proteins, which includes AopP from Aeromonas salmonicida. Aeromonas species are known to cause gastrointestinal disease in humans, and are associated mainly with subcutaneous wound infections and septicaemia in other metazoans, particularly fish. AopP has been reported to have inhibitory activity against the NF‐κB pathway in cultured cells, although the pathological out... Cellular Microbiology journals http://www.medworm.com/rss/comments.php?id=5437732 Mon, 31 Oct 2011 04:00:00 +0100 5437732 http://www.medworm.com/index.php?rid=5376564&cid=s_32061_77_f&fid=32061&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1462-5822.2011.01717.x AbstractSome pathogens are able to establish themselves within the host because they have evolved mechanisms to disrupt host innate immunity. For example, a number of pathogens secrete preformed effector proteins via type III secretion apparati that influence innate immune or apoptotic signaling pathways. One group of effector proteins that usurp innate immune signaling is the YopJ‐like family of bacterial effector proteins, which includes AopP from Aeromonas salmonicida. Aeromonas species are known to cause gastrointestinal disease in humans, and are associated mainly with subcutaneous wound infections and septicemia in other metazoans, particularly fish. AopP has been reported to have inhibitory activity against the NF‐κB pathway in cultured cells, although the pathological outcomes... Cellular Microbiology journals http://www.medworm.com/rss/comments.php?id=5376564 Mon, 31 Oct 2011 04:00:00 +0100 5376564 http://www.medworm.com/index.php?rid=5356034&cid=s_32061_77_f&fid=32061&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1462-5822.2011.01716.x SummaryBurkholderia cenocepacia is a Gram‐negative opportunistic pathogen in patients with cystic fibrosis and chronic granulomatous disease. The bacterium survives intracellularly in macrophages within a membrane‐bound vacuole (BcCV) that precludes the fusion with lysosomes. The underlying cellular mechanisms and bacterial molecules mediating these phenotypes are unknown. Here, we show that intracellular B. cenocepacia expressing a type VI secretion system (T6SS) targets the activation of the Rac1 and Cdc42 RhoGTPase by reducing the cellular pool of GTP‐bound Rac1 and Cdc42. The T6SS also increases the cellular pool of GTP‐bound RhoA and decreases cofilin activity. These effects lead to abnormal actin polymerization causing collapse of lamellipodia and failure to retract the uropo... Cellular Microbiology journals http://www.medworm.com/rss/comments.php?id=5356034 Fri, 28 Oct 2011 07:25:42 +0100 5356034 http://www.medworm.com/index.php?rid=5418549&cid=s_32061_77_f&fid=32061&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1462-5822.2011.01716.x SummaryBurkholderia cenocepacia is a Gram‐negative opportunistic pathogen of patients with cystic fibrosis and chronic granulomatous disease. The bacterium survives intracellularly in macrophages within a membrane‐bound vacuole (BcCV) that precludes the fusion with lysosomes. The underlying cellular mechanisms and bacterial molecules mediating these phenotypes are unknown. Here, we show that intracellular B. cenocepacia expressing a type VI secretion system (T6SS) affects the activation of the Rac1 and Cdc42 RhoGTPase by reducing the cellular pool of GTP‐bound Rac1 and Cdc42. The T6SS also increases the cellular pool of GTP‐bound RhoA and decreases cofilin activity. These effects lead to abnormal actin polymerization causing collapse of lamellipodia and failure to retract the uro... Cellular Microbiology journals http://www.medworm.com/rss/comments.php?id=5418549 Tue, 25 Oct 2011 04:00:00 +0100 5418549 http://www.medworm.com/index.php?rid=5356035&cid=s_32061_77_f&fid=32061&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1462-5822.2011.01715.x In this study, we explored the mechanisms that enable B. cenocepacia to survive inside macrophages. We found that B. cenocepacia disrupts the actin cytoskeleton of infected macrophages, drastically altering their morphology. Submembranous actin undergoes depolymerization, leading to cell retraction. The bacteria perturb actin architecture by inactivating Rho‐family GTPases, particularly Rac1 and Cdc42. GTPase inactivation follows internalization of viable B. cenocepacia and compromises phagocyte function: macropinocytosis and phagocytosis are markedly inhibited, likely impairing the microbicidal and antigen‐presenting capability of infected macrophages. The type VI secretion system is essential for the bacteria to elicit these changes. This is the first report demonstrating inactivatio... Cellular Microbiology journals http://www.medworm.com/rss/comments.php?id=5356035 Tue, 25 Oct 2011 04:00:00 +0100 5356035 http://www.medworm.com/index.php?rid=5321944&cid=s_32061_77_f&fid=32061&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1462-5822.2011.01699.x (Source: Cellular Microbiology) Cellular Microbiology journals http://www.medworm.com/rss/comments.php?id=5321944 Sun, 16 Oct 2011 17:16:11 +0100 5321944 http://www.medworm.com/index.php?rid=5321941&cid=s_32061_77_f&fid=32061&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1462-5822.2011.01714.x This study was performed to elucidate the host cell scaffolding and signaling molecules that Campylobacter jejuni utilizes to invade epithelial cells. We hypothesized that the C. jejunifibronectin‐binding proteins and secreted proteins are required for cell signaling and maximal invasion of host cells. C. jejuni binding to host cells via the CadF and FlpAFibronectin‐binding proteins activated the epidermal growth factor (EGF) pathway, as evidenced by inhibitor studies and immunoprecipitation coupled with immunoblot analysis using antibodies reactive against total and active EGF receptor. Inhibitor studies revealed maximal C. jejuni host cell invasion was dependent upon PI3‐Kinase, c‐Src, and focal adhesion kinase (FAK), all of which are known to participate in cytoskeletal rearrang... Cellular Microbiology journals http://www.medworm.com/rss/comments.php?id=5321941 Sun, 16 Oct 2011 17:15:17 +0100 5321941 http://www.medworm.com/index.php?rid=5321942&cid=s_32061_77_f&fid=32061&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1462-5822.2011.01712.x In conclusion, this study demonstrates that the most relevant pulmonary pathogen S. pneumoniae induces release of pro‐inflammatory and pro‐coagulative components directly contributing to pathophysiological processes leading to fatal tissue injury during course of infection. (Source: Cellular Microbiology) Cellular Microbiology journals http://www.medworm.com/rss/comments.php?id=5321942 Fri, 14 Oct 2011 04:00:00 +0100 5321942 http://www.medworm.com/index.php?rid=5311594&cid=s_32061_77_f&fid=32061&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1462-5822.2011.01713.x SummaryLegionella pneumophila is a facultative intracellular pathogen capable of replicating in a wide spectrum of cells. Successful infection by Legionella requires the Dot/Icm type IV secretion system, which translocates a large number of effector proteins into infected cells. By co‐opting numerous host cellular processes, these proteins function to establish a specialized organelle that allows bacterial survival and proliferation. Even within the vacuole, L. pneumophila triggers robust immune responses. Recent studies reveal that a subset of Legionella effectors directly target some basic components of the host innate immunity systems such as phagosome maturation. Others play essential roles in engaging the host innate immune surveillance system. This review will highlight recent prog... Cellular Microbiology journals http://www.medworm.com/rss/comments.php?id=5311594 Tue, 11 Oct 2011 04:00:00 +0100 5311594 http://www.medworm.com/index.php?rid=5397544&cid=s_32061_77_f&fid=32061&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1462-5822.2011.01710.x SummaryLegionella pneumophila, the causative agent of Legionnaires' disease, infects and replicates in macrophages and amoebas. Following internalization, L. pneumophila resides in a vacuole structure called Legionella‐containing vacuole (LCV). The LCV escapes from the endocytic maturation process and avoids fusion with the lysosome, a hallmark of Legionella pathogenesis. Interference with the secretory vesicle transport and avoiding lysosomal targeting render the LCV permissive for L. pneumophila intracellular replication. Central to L. pneumophila pathogenesis is a defect in the organelle trafficking/intracellular multiplication (Dot/Icm) type IV secretion system that translocates a large number of effector proteins into host cells. Many of the Dot/Icm effectors employ diverse an... Cellular Microbiology journals http://www.medworm.com/rss/comments.php?id=5397544 Mon, 10 Oct 2011 04:00:00 +0100 5397544 http://www.medworm.com/index.php?rid=5397543&cid=s_32061_77_f&fid=32061&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1462-5822.2011.01711.x SummaryHuman pathogenic Bartonella henselae cause cat scratch disease and vasculoproliferative disorders. An important pathogenicity factor of B. henselae is the trimeric autotransporter adhesin Bartonella adhesin A (BadA) which is modularly constructed and consists of a head, a long and repetitive neck‐stalk module with 22 repetitive neck/stalk repeats and a membrane anchor. The BadA head is crucial for bacterial adherence to host cells, binding to several extracellular matrix proteins and for the induction of vascular endothelial growth factor (VEGF) secretion. Here, we analysed the biological role of the BadA stalk in the infection process in greater detail. For this purpose, BadA head‐bearing and headless deletion mutants with different lengths (containing one or four neck/stalk ... Cellular Microbiology journals http://www.medworm.com/rss/comments.php?id=5397543 Mon, 10 Oct 2011 04:00:00 +0100 5397543 http://www.medworm.com/index.php?rid=5302089&cid=s_32061_77_f&fid=32061&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1462-5822.2011.01708.x AbstractThe IRG protein Irgm3 preserves cell survival during coxsackievirus B3 (CVB3) infection. However, the molecular mechanisms are not clear. Here, we examined the effect of Irgm3 expression on ER stress triggered by pharmacological agents or CVB3 infection. In Tet‐On/Irgm3 HeLa cells, Irgm3 expression suppressed either chemical‐ or CVB3‐induced upregulation of glucose‐regulated protein78. Further, Irgm3 strongly inhibited the activation of both the PERK and ATF6 pathways of ER stress responses, which further led to the diminished phosphorylation of eIF2α, reduced cleavage/activation of transcription factor SREBP1 and attenuated induction of proapoptotic genes CHOP and GADD34. These data were further supported by experiments using Irgm3 knockout mouse embryonic fibroblasts, in... Cellular Microbiology journals http://www.medworm.com/rss/comments.php?id=5302089 Mon, 10 Oct 2011 04:00:00 +0100 5302089 http://www.medworm.com/index.php?rid=5302088&cid=s_32061_77_f&fid=32061&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1462-5822.2011.01709.x SummaryMarburg virus (MARV) matrix protein VP40 plays a key role in virus assembly, recruiting nucleocapsids and the surface protein GP to filopodia, the sites of viral budding. In addition, VP40 is the only MARV protein able to induce the release of filamentous virus‐like particles (VLPs) indicating its function in MARV budding. Here, we demonstrated that VP40 is phosphorylated and that tyrosine residues at positions 7, 10, 13 and 19 represent major phosphorylation acceptor sites. Mutagenesis of these tyrosine residues resulted in expression of a non‐phosphorylatable form of VP40 (VP40mut). VP40mut was able to bind to cellular membranes, produce filamentous VLPs, and inhibit interferon‐induced gene expression similarly to wild type VP40. However, VP40mut was specifically impaired in... Cellular Microbiology journals http://www.medworm.com/rss/comments.php?id=5302088 Mon, 10 Oct 2011 04:00:00 +0100 5302088 http://www.medworm.com/index.php?rid=5302087&cid=s_32061_77_f&fid=32061&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1462-5822.2011.01710.x SummaryLegionella pneumophila, the causative agent of Legionnaires’ disease, infects and replicates in macrophages and amoebas. Following internalization, L. pneumophila resides in a vacuole structure called Legionella‐containing vacuole (LCV). The LCV escapes from the endocytic maturation process and avoids fusion with the lysosome, a hallmark of Legionella pathogenesis. Interference with the secretory vesicle transport and avoiding lysosomal targeting render the LCV permissive for L. pneumophila intracellular replication. Central to L. pneumophila pathogenesis is a defect in the organelle trafficking/intracellular multiplication (Dot/Icm) type IV secretion system that translocates a large number of effector proteins into host cells. Many of the Dot/Icm effectors employ diverse and so... Cellular Microbiology journals http://www.medworm.com/rss/comments.php?id=5302087 Mon, 10 Oct 2011 04:00:00 +0100 5302087 http://www.medworm.com/index.php?rid=5311593&cid=s_32061_77_f&fid=32061&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1462-5822.2011.01707.x SummaryMembers of the Nucleotide‐binding, oligomerization domain (NOD)‐like receptor (NLR) proteins assemble into a multiprotein platform, known as the inflammasome, to induce caspase‐1 activation followed by the subsequent secretion of IL‐1β and IL‐18. In this review, we focus on the role of NLRs in inflammasome activation as part of the host defense against bacterial pathogens. One of activators of the NLRC4 inflammasome is bacterial flagellin secreted through type III or IV secretion systems, which are important for the pathogenicity of many Gram‐negative bacteria. The NLRP3 inflammasome is mainly activated by a large number of bacterial pore‐forming toxins. Despite our knowledge of inflammasome activation upon bacterial infection, the function of antibacterial defense un... Cellular Microbiology journals http://www.medworm.com/rss/comments.php?id=5311593 Sat, 01 Oct 2011 04:00:00 +0100 5311593 http://www.medworm.com/index.php?rid=5302086&cid=s_32061_77_f&fid=32061&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1462-5822.2011.01711.x AbstractHuman pathogenic Bartonella henselae cause cat scratch disease and vasculoproliferative disorders. An important pathogenicity factor of B. henselae is the trimeric autotransporter adhesin Bartonella adhesin A (BadA) which is modularly constructed and consists of a head, a long and repetitive neck‐stalk module with 22 repetitive neck/stalk repeats and a membrane anchor. The BadA head is crucial for bacterial adherence to host cells, binding to several extracellular matrix proteins and for the induction of vascular endothelial growth factor (VEGF) secretion. Here, we analyzed the biological role of the BadA stalk in the infection process in greater detail. For this purpose, BadA head‐bearing and headless deletion mutants with different lengths (containing one or four neck/stalk r... Cellular Microbiology journals http://www.medworm.com/rss/comments.php?id=5302086 Sat, 01 Oct 2011 04:00:00 +0100 5302086 http://www.medworm.com/index.php?rid=5269767&cid=s_32061_77_f&fid=32061&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1462-5822.2011.01706.x SummaryEnteroaggregative Escherichia coli (EAEC) induces release of pro‐inflammatory markers and disruption of intestinal epithelial barriers in vitro suggesting an inflammatory aspect to EAEC infection. However, the mechanisms underlying EAEC‐induced mucosal inflammatory responses and the extent to which these events contribute to pathogenesis is not well characterized. Employing an established in vitro model we demonstrated that EAEC prototype strain 042 induces migration of polymorphonuclear neutrophils (PMNs) across polarized T84 cell monolayers. This event was mediated through a conserved host cell signaling cascade involving the 12/15‐LOX pathway and led to apical secretion of an arachidonic acid‐derived lipid PMN chemoattractant, guiding PMNs across the epithelia to the site... Cellular Microbiology journals http://www.medworm.com/rss/comments.php?id=5269767 Sat, 01 Oct 2011 01:28:53 +0100 5269767 http://www.medworm.com/index.php?rid=5397545&cid=s_32061_77_f&fid=32061&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1462-5822.2011.01704.x SummaryPseudomonas aeruginosa causes chronic lung infections in the airways of cystic fibrosis (CF) patients. Psl is an extracellular polysaccharide expressed by non‐mucoid P. aeruginosa strains, which are believed to be initial colonizers. We hypothesized that Psl protects P. aeruginosa from host defences within the CF lung prior to their conversion to the mucoid phenotype. We discovered that serum opsonization significantly increased the production of reactive oxygen species (ROS) by neutrophils exposed to a psl‐deficient mutant, compared with wild‐type (WT) and Psl overexpressing strains (Psl++). Psl‐deficient P. aeruginosa were internalized and killed by neutrophils and macrophages more efficiently than WT and Psl++ variants. Deposition of complement components C3, C5 and... Cellular Microbiology journals http://www.medworm.com/rss/comments.php?id=5397545 Tue, 27 Sep 2011 04:00:00 +0100 5397545 http://www.medworm.com/index.php?rid=5269770&cid=s_32061_77_f&fid=32061&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1462-5822.2011.01703.x SummarySmall molecular weight GTPases are master regulators of eukaryotic signaling, making them prime targets for bacterial virulence factors. Here, we review the recent advances made in understanding how bacterial type III secreted effector proteins directly activate GTPase signaling cascades. Specifically we focus on the SopE/WxxxE family of effectors that functionally mimic guanine nucleotide exchange factors (GEFs): the endogenous activators of Rho‐family GTPases. Recent structural and biochemical studies have provided keen insight into both the signaling potency and substrate specificity of bacterial GEFs. Additionally, these bacterial GEFs display fascinating cell biological properties that provide insight into both host cell physiology and infectious disease strategies. (Source: ... Cellular Microbiology journals http://www.medworm.com/rss/comments.php?id=5269770 Tue, 27 Sep 2011 04:00:00 +0100 5269770 http://www.medworm.com/index.php?rid=5269769&cid=s_32061_77_f&fid=32061&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1462-5822.2011.01704.x SummaryPseudomonas aeruginosa causes chronic lung infections in the airways of cystic fibrosis (CF) patients. Psl is an extracellular polysaccharide expressed by nonmucoid P. aeruginosa strains,which are believed to be initial colonizers. We hypothesized that Psl protects P. aeruginosa from host defenses within the CF lung prior to their conversion to the mucoid phenotype. We discovered that serum opsonization significantly increased the production of reactive oxygen species (ROS) by neutrophils exposed to a psl‐deficient mutant, compared to wild type (WT) and Psl over‐expressing strains (Psl++). Psl‐deficient P. aeruginosa were internalized and killed by neutrophils and macrophages more efficiently than WT and Psl++variants. Deposition of complement components C3, C5, and C7 was sig... Cellular Microbiology journals http://www.medworm.com/rss/comments.php?id=5269769 Tue, 27 Sep 2011 04:00:00 +0100 5269769 http://www.medworm.com/index.php?rid=5269768&cid=s_32061_77_f&fid=32061&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1462-5822.2011.01705.x SummarySevere infectious diseases remain a major and life‐threatening health problem. In serious cases a systemic activation of the coagulation cascade and hypovolemic shock are critical complications that are associated with high mortality rates. Here we report that blood mononuclear cells, stimulated with M1 protein of Streptococcus pyogenes or other bacterial virulence factors, produce not only pro‐coagulant, but also pro‐inflammatory microparticles (MPs). Our results also show that activation of the contact system on MPs contributes to these two effects. Phosphatidylserine (PS) plays an important role in these processes as its up‐regulation on MPs allows an assembly and activation of the contact system. This in turn results in stabilization of the tissue factor‐induced clot a... Cellular Microbiology journals http://www.medworm.com/rss/comments.php?id=5269768 Tue, 27 Sep 2011 04:00:00 +0100 5269768 http://www.medworm.com/index.php?rid=5246936&cid=s_32061_77_f&fid=32061&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1462-5822.2011.01702.x SummaryMycoplasma hyopneumoniae is a major, economically‐damaging respiratory pathogen. Although M. hyopneumoniae cells bind plasminogen, the identification of plasminogen‐binding surface proteins and biological ramifications of acquiring plasminogen requires further investigation. mhp182 encodes a highly expressed 102 kDa protein (P102) that undergoes proteolytic processing to generate surface‐located N‐terminal 60 kDa (P60) and C‐terminal 42 kDa (P42) proteins of unknown function. We show that recombinant P102 (rP102) binds plasminogen at physiologically relevant concentrations (KD∼ 76 nM) increasing the susceptibility of plasmin(ogen) to activation by tissue‐specific plasminogen activator (tPA). Recombinant proteins constructed to mimic P60 (rP60) and P42 (rP42) also bound... Cellular Microbiology journals http://www.medworm.com/rss/comments.php?id=5246936 Fri, 23 Sep 2011 15:14:36 +0100 5246936 http://www.medworm.com/index.php?rid=5218242&cid=s_32061_77_f&fid=32061&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1462-5822.2011.01698.x (Source: Cellular Microbiology) Cellular Microbiology journals http://www.medworm.com/rss/comments.php?id=5218242 Wed, 14 Sep 2011 11:28:17 +0100 5218242 http://www.medworm.com/index.php?rid=5204879&cid=s_32061_77_f&fid=32061&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1462-5822.2011.01700.x In this study, we show that Francisella novicida escapes into the cytosol of bone marrow‐derived dendritic cells (BMDC) where it undergoes rapid replication. We show that F. novicida activates the AIM2 inflammasome in BMDC, causing release of large amounts of IL‐1β and rapid host cell death. The Francisella Pathogenicity Island is required for bacterial escape and replication and for inflammasome activation in dendritic cells. In addition, we show that bacterial DNA is bound by AIM2, which leads to inflammasome assembly in infected dendritic cells. IFN‐β is upregulated in BMDC following Francisella infection, and the IFN‐β signaling pathway is partially required for inflammasome activation in this cell type. Taken together, our results demonstrate that F. novicida induces inflam... Cellular Microbiology journals http://www.medworm.com/rss/comments.php?id=5204879 Thu, 08 Sep 2011 04:00:00 +0100 5204879 http://www.medworm.com/index.php?rid=5376565&cid=s_32061_77_f&fid=32061&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1462-5822.2011.01695.x This study was designed to clarify the cross‐talk between recognition and phagocytosis of microbes in dendritic cells. The murine dendritic cell line XS106 cells were stimulated with the murine C‐type lectin SIGNR1 ligand lipoarabinomannan and the Toll‐like receptor 2 ligand FSL‐1. The co‐stimulation significantly suppressed FSL‐1‐mediated activation of NF‐κB as well as production of TNF‐α, IL‐6 and IL‐12p40 in a dose‐dependent manner. The suppression was significantly but not completely recovered by knock‐down of SIGNR1. SIGNR1 was associated with Toll‐like receptor 2 in XS106 cells. The co‐stimulation upregulated the expression of suppressor of cytokine signalling‐1 in XS106 cells, the knock‐down of which almost completely recovered the suppression of ... Cellular Microbiology journals http://www.medworm.com/rss/comments.php?id=5376565 Wed, 07 Sep 2011 04:00:00 +0100 5376565 http://www.medworm.com/index.php?rid=5321943&cid=s_32061_77_f&fid=32061&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1462-5822.2011.01683.x SummaryHuman FACT (facilitates chromatin transcription) consists of the proteins SPT16 and SSRP1 and acts as a histone chaperone in the (dis)assembly of nucleosome (and thereby chromatin) structure during transcription and DNA replication. We identified a Plasmodium berghei protein, termed FACT‐L, with homology to the SPT16 subunit of FACT. Epitope tagging of FACT‐L showed nuclear localization with high expression in the nuclei of (activated) male gametocytes. The gene encoding FACT‐L could not be deleted indicating an essential role during blood‐stage development. Using a ‘promoter‐swap’ approach whereby the fact‐l promoter was replaced by an ‘asexual blood stage‐specific’ promoter that is silent in gametocytes, transcription of fact‐l in promoter‐swap mutant gam... Cellular Microbiology journals http://www.medworm.com/rss/comments.php?id=5321943 Wed, 07 Sep 2011 04:00:00 +0100 5321943 http://www.medworm.com/index.php?rid=5269771&cid=s_32061_77_f&fid=32061&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1462-5822.2011.01697.x SummaryAdaptation to environmental stress is a key process that allows the unicellular parasite Entamoeba histolytica to survive in its human host. We previously characterized EhMLBP as an essential protein for the growth and the virulence of the parasite. EhMLBP binds to methylated repetitive DNA, and is one of the core proteins of the parasite's epigenetic machinery. Here, we show that EhMLBP and heat shock proteins have common properties. EhMLBP is induced by heat shock and its expression is regulated by a heat shock element binding site that is located in its 5′ non‐coding region. Following heat shock, the perinuclear localization of EhMLBP in control trophozoites is replaced by an even distribution within the nucleus alongside with an enhanced recruitment of EhMLBP to the reverse ... Cellular Microbiology journals http://www.medworm.com/rss/comments.php?id=5269771 Wed, 07 Sep 2011 04:00:00 +0100 5269771 http://www.medworm.com/index.php?rid=5246937&cid=s_32061_77_f&fid=32061&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1462-5822.2011.01682.x In conclusion, H. suis and H. pylori GGT‐mediated generation of pro‐oxidant glutathione degradation products brings on cell damage and causes apoptosis or necrosis, dependent on the amount of extracellular glutathione available as a GGT substrate. (Source: Cellular Microbiology) Cellular Microbiology journals http://www.medworm.com/rss/comments.php?id=5246937 Wed, 07 Sep 2011 04:00:00 +0100 5246937 http://www.medworm.com/index.php?rid=5204891&cid=s_32061_77_f&fid=32061&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1462-5822.2011.01679.x ABSTRACTThe influenza virus establishes close functional and structural connections with the nucleus of the infected cell. Thus, viral ribonucleoproteins (RNPs) are closely bound to chromatin components and the main constituent of viral RNPs, the NP protein, interacts with histone tails. Using a yeast two‐hybrid screening, we previously found that the PA influenza virus polymerase subunit interacts with the CHD6 protein, a member of the CHD family of chromatin remodelers. Here we show that CHD6 also interacts with the viral polymerase complex and colocalizes with viral RNPs in the infected cells. To study the relationships between RNPs, chromatin and CHD6, we have analyzed whether NP and CHD6 binds to peptides representing trimethylated lysines of histone 3 tails that mark transcriptiona... Cellular Microbiology journals http://www.medworm.com/rss/comments.php?id=5204891 Wed, 07 Sep 2011 04:00:00 +0100 5204891 http://www.medworm.com/index.php?rid=5204890&cid=s_32061_77_f&fid=32061&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1462-5822.2011.01680.x AbstractThe phosphatidylinositol‐3‐kinase (PI3K) was identified to be activated upon influenza A virus infection. An early and transient induction of PI3K signaling is caused by viral attachment to cells and promotes virus entry. In later phases of infection the kinase is activated by the viral NS1 protein to prevent premature apoptosis. Besides these virus supporting functions, it was suggested that PI3K signaling is involved in dsRNA and IAV induced antiviral responses by enhancing the activity of interferon regulatory factor‐3 (IRF‐3). However, molecular mechanisms of activation remained obscure. Here we show that accumulation of vRNA in cells infected with influenza A or B viruses results in PI3K activation. Furthermore, expression of the RNA receptors Rig‐I and MDA5 was incr... Cellular Microbiology journals http://www.medworm.com/rss/comments.php?id=5204890 Wed, 07 Sep 2011 04:00:00 +0100 5204890 http://www.medworm.com/index.php?rid=5204889&cid=s_32061_77_f&fid=32061&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1462-5822.2011.01681.x SummaryThe encystation process is a key step in Toxoplasma gondii life cycle, allowing the parasite to escape from the host immune system and the transmission among the hosts. A detailed characterization of the formation and structure of the cyst stage is essential for a better knowledge of toxoplasmosis. Here we isolated cysts from mice brains and analyzed the cyst wall structure and cyst matrix organization using different electron microscopy techniques. Images obtained showed that the cyst wall presented a filamentous aspect, with circular openings on its surface. The filaments were organized in two layers: a compact one, facing the exterior of the whole cyst and a more loosen one, facing the matrix. Within the cyst wall, we observed tubules and a large number of vesicles. The cyst matr... Cellular Microbiology journals http://www.medworm.com/rss/comments.php?id=5204889 Wed, 07 Sep 2011 04:00:00 +0100 5204889 http://www.medworm.com/index.php?rid=5204888&cid=s_32061_77_f&fid=32061&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1462-5822.2011.01682.x In conclusion, H. suis and H. pylori GGT‐mediated generation of pro‐oxidant glutathione degradation products brings on cell damage and causes apoptosis or necrosis, dependent on the amount of extracellular glutathione available as a GGT substrate. (Source: Cellular Microbiology) Cellular Microbiology journals http://www.medworm.com/rss/comments.php?id=5204888 Wed, 07 Sep 2011 04:00:00 +0100 5204888 http://www.medworm.com/index.php?rid=5204887&cid=s_32061_77_f&fid=32061&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1462-5822.2011.01683.x AbstractHuman FACT (facilitates chromatin transcription) consists of the proteins SPT16 and SSRP1 and acts as a histone chaperone in the (dis)assembly of nucleosome (and thereby chromatin) structure during transcription and DNA replication. We identified a Plasmodium berghei protein, termed FACT‐L, with homology to the SPT16 subunit of FACT. Epitope tagging of FACT‐L showed nuclear localisation with high expression in the nuclei of (activated) male gametocytes. The gene encoding FACT‐L could not be deleted indicating an essential role during blood stage development. Using a ′promoter‐swap′ approach whereby the fact‐l promoter was replaced by an ′asexual blood stage‐specific′ promoter that is silent in gametocytes, transcription of fact‐l in promoter‐swap mutant game... Cellular Microbiology journals http://www.medworm.com/rss/comments.php?id=5204887 Wed, 07 Sep 2011 04:00:00 +0100 5204887 http://www.medworm.com/index.php?rid=5204886&cid=s_32061_77_f&fid=32061&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1462-5822.2011.01684.x SummaryShiga toxin‐producing bacteria cause widespread outbreaks of bloody diarrhea that may progress to life‐threatening systemic complications. Shiga toxins (Stxs), the main virulence factors expressed by the pathogens, are ribosome‐inactivating proteins which inhibit protein synthesis by removing an adenine residue from 28S rRNA. Recently, Stxs were shown to activate multiple stress‐associated signaling pathways in mammalian cells. The ribotoxic stress response is activated following the depurination reaction localized to the α‐sarcin/ricin loop of eukaryotic ribosomes. The unfolded protein response (UPR) may be initiated by toxin unfolding within the endoplasmic reticulum, and maintained by production of truncated, misfolded proteins following intoxication. Activation of the... Cellular Microbiology journals http://www.medworm.com/rss/comments.php?id=5204886 Wed, 07 Sep 2011 04:00:00 +0100 5204886 http://www.medworm.com/index.php?rid=5204885&cid=s_32061_77_f&fid=32061&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1462-5822.2011.01685.x SUMMARYNon‐enveloped picornavirus echovirus 1 (EV1) clusters its receptor α2β1 integrin and causes their internalization and accumulation in α2β1 integrin enriched multivesicular bodies (α2‐MVBs). Our results here show that these α2‐MVBs are distinct from acidic late endosomes/lysosomes by several criteria: 1) live intra endosomal pH measurements show that α2‐MVBs are not acidic, 2) they are not positive for the late endosomal marker LBPA or Dil‐LDL internalized to lysosomes, and 3) simultaneous stimulation of epidermal growth factor receptor (EGFR) and α2β1 integrin clustering leads to their accumulation in separate endosomes. EGFR showed down‐regulation between 15 min and 2 h, whereas accumulation of α2β1 integrin/EV1 led to an increase of integrin fluorescence in ... Cellular Microbiology journals http://www.medworm.com/rss/comments.php?id=5204885 Wed, 07 Sep 2011 04:00:00 +0100 5204885 http://www.medworm.com/index.php?rid=5204884&cid=s_32061_77_f&fid=32061&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1462-5822.2011.01686.x AbstractFunctional analysis of Plasmodium genes by classical reverse genetics is currently limited to mutants that are viable during erythrocytic schizogony, the pathogenic phase of the malaria parasite where transfection is performed. Here, we describe a conceptually simple experimental approach to study the function of genes essential to the asexual blood stages in a subsequent life cycle stage by a promoter swap approach. As a proof of concept we targeted the unconventional class XIV myosin MyoA, which is known to be required for Toxoplasma gondii tachyzoite locomotion and host cell invasion. By placing the corresponding Plasmodium berghei gene, PbMyoA, under the control of the apical membrane antigen 1 (AMA1) promoter, expression in blood stages is maintained but switched off during tr... Cellular Microbiology journals http://www.medworm.com/rss/comments.php?id=5204884 Wed, 07 Sep 2011 04:00:00 +0100 5204884 http://www.medworm.com/index.php?rid=5204883&cid=s_32061_77_f&fid=32061&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1462-5822.2011.01693.x AbstractIn human disease induced by Salmonella enterica serovar Typhimurium (S. Typhimurium), transepithelial migration of neutrophils rapidly follows attachment of the bacteria to the epithelial apical membrane. We have previously shown that during S. Typhimurium infection the multidrug resistance associated protein 2 (MRP2) is highly expressed at the apical surface of the intestinal epithelia, and that it functions as an efflux pump for the potent neutrophil chemoattractant hepoxilin A3. However, the molecular mechanisms regulating its apical localization during active states of inflammation remain unknown. Thus, our objective was to determine the mechanistic basis for the translocation of MRP2 to the apical surface of intestinal epithelial cells during S. Typhimurium infection. We show ... Cellular Microbiology journals http://www.medworm.com/rss/comments.php?id=5204883 Wed, 07 Sep 2011 04:00:00 +0100 5204883 http://www.medworm.com/index.php?rid=5204882&cid=s_32061_77_f&fid=32061&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1462-5822.2011.01694.x In conclusion, the results demonstrated that Salmonella AvrA modulates survival of infected macrophages likely via JNK suppression, and prevents macrophage death and rapid bacterial dissemination. AvrA suppression of apoptosis in infected macrophages may allow for establishment of a stable intracellular niche typical of intracellular pathogens. (Source: Cellular Microbiology) Cellular Microbiology journals http://www.medworm.com/rss/comments.php?id=5204882 Wed, 07 Sep 2011 04:00:00 +0100 5204882 http://www.medworm.com/index.php?rid=5204881&cid=s_32061_77_f&fid=32061&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1462-5822.2011.01695.x This study was designed to clarify the crosstalk between recognition and phagocytosis of microbes in dendritic cells. The murine dendritic cell line XS106 cells were stimulated with the murine C‐type lectin SIGNR1 ligand lipoarabinomannan and the Toll‐like receptor 2 ligand FSL‐1. The costimulation significantly suppressed FSL‐1‐mediated activation of NF‐κB as well as production of TNF‐α, IL‐6 and IL‐12p40 in a dose‐dependent manner. The suppression was significantly but not completely recovered by knockdown of SIGNR1. SIGNR1 was associated with Toll‐like receptor 2 in XS106 cells. The costimulation upregulated the expression of suppressor of cytokine signaling‐1 in XS106 cells, the knockdown of which almost completely recovered the suppression of the FSL‐1‐me... Cellular Microbiology journals http://www.medworm.com/rss/comments.php?id=5204881 Wed, 07 Sep 2011 04:00:00 +0100 5204881 http://www.medworm.com/index.php?rid=5204880&cid=s_32061_77_f&fid=32061&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1462-5822.2011.01697.x SummaryAdaptation to environmental stress is a key process that allows the unicellular parasite Entamoeba histolytica to survive in its human host. We previously characterized EhMLBP as an essential protein for the growth and the virulence of the parasite. EhMLBP binds to methylated repetitive DNA, and is one of the core proteins of the parasite's epigenetic machinery. Here, we show that EhMLBP and heat shock proteins have common properties. EhMLBP is induced by heat shock and its expression is regulated by a heat shock element binding site that is located in its 5′ non‐coding region. Following heat shock, the perinuclear localization of EhMLBP in control trophozoites is replaced by an even distribution within the nucleus alongside with an enhanced recruitment of EhMLBP to the reverse ... Cellular Microbiology journals http://www.medworm.com/rss/comments.php?id=5204880 Wed, 07 Sep 2011 04:00:00 +0100 5204880 http://www.medworm.com/index.php?rid=5204878&cid=s_32061_77_f&fid=32061&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1462-5822.2011.01701.x SummarySalmonella enterica serovar Typhimurium (S. Typhimurium) is a Gram‐negative facultative foodborne pathogen that causes gastroenteritis in humans. This bacterium has evolved a sophisticated machinery to alter host cell function critical to its virulence capabilities. Central to S. Typhimurium pathogenesis are two Type three secretion systems (T3SS) encoded within pathogenicity islands SPI‐1 and SPI‐2 that are responsible for the secretion and translocation of a set of bacterial proteins termed effectors into host cells with the intention of altering host cell physiology for bacterial entry and survival. Thus, once delivered by the T3SS, the secreted effectors play critical roles in manipulating the host cell to allow for bacteria invasion, induction of inflammatory responses, a... Cellular Microbiology journals http://www.medworm.com/rss/comments.php?id=5204878 Thu, 01 Sep 2011 04:00:00 +0100 5204878 http://www.medworm.com/index.php?rid=5156635&cid=s_32061_77_f&fid=32061&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1462-5822.2011.01638.x (Source: Cellular Microbiology) Cellular Microbiology journals http://www.medworm.com/rss/comments.php?id=5156635 Thu, 25 Aug 2011 10:17:20 +0100 5156635 http://www.medworm.com/index.php?rid=5156634&cid=s_32061_77_f&fid=32061&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1462-5822.2011.01643.x SummaryIntracellular bacterial pathogens Francisella novicida and the Live Vaccine Strain (LVS) are recognized in the macrophage cytosol by the AIM2 inflammasome, which leads to the activation of caspase‐1 and the processing and secretion of active IL‐1β, IL‐18 and pyroptosis. Previous studies have reported that F. novicida and LVS mutants in specific genes (e.g. FTT0584, mviN and ripA) induce elevated inflammasome activation and hypercytotoxicity in host cells, leading to the proposal that F. novicida and LVS may have proteins that actively modulate inflammasome activation. However, there has been no direct evidence of such inflammasome evasion mechanisms. Here, we demonstrate for the first time that the above mutants, along with a wide range of F. novicida hypercytotoxic mut... Cellular Microbiology journals http://www.medworm.com/rss/comments.php?id=5156634 Tue, 23 Aug 2011 23:00:00 +0100 5156634 http://www.medworm.com/index.php?rid=5218239&cid=s_32061_77_f&fid=32061&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1462-5822.2011.01666.x In this study we found that EspT induces expression of the pro‐inflammatory mediators cyclooxygenase‐2 (COX‐2) an enzyme involved in production of prostaglandin E(2) (PGE2), interleukin (Il)‐8 and Il‐1β in U937 human macrophages by activating the nuclear factor kappa‐B (NF‐κB), the extracellular signal‐regulated kinases 1 and 2 (Erk1/2) and c‐Jun N‐terminal kinase (JNK) pathways. Since EspT modulates the activation of Cdc42 and Rac1, which mediates bacterial invasion into epithelial cells, we investigated the involvement of these Rho GTPases and bacterial invasion on pro‐inflammatory responses and found that (i) Rac1, but not Cdc42, is involved in EspT‐induced Il‐8 and Il‐1β secretion and (ii) cytochalasin D inhibits EspT‐induced EPEC invasion into U937 but... Cellular Microbiology journals http://www.medworm.com/rss/comments.php?id=5218239 Tue, 16 Aug 2011 04:00:00 +0100 5218239 http://www.medworm.com/index.php?rid=5138012&cid=s_32061_77_f&fid=32061&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1462-5822.2011.01665.x AbstractBiotrophic and hemibiotrophic fungi are successful groups of plant pathogens that require living plant tissue to survive and complete their life cycle. Members of these groups include the rust fungi and powdery mildews and species in the Ustilago, Cladosporium and Magnaporthe genera. Collectively, they represent some of the most destructive plant parasites, causing huge economic losses and threatening global food security. During plant infection, pathogens synthesise and secrete effector proteins, some of which are translocated into the plant cytosol where they can alter the host's response to the invading pathogen. In a successful infection, pathogen effectors facilitate suppression of the plant's immune system and orchestrate the reprogramming of the infected tissue so that it be... Cellular Microbiology journals http://www.medworm.com/rss/comments.php?id=5138012 Mon, 15 Aug 2011 23:00:00 +0100 5138012 http://www.medworm.com/index.php?rid=5218240&cid=s_32061_77_f&fid=32061&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1462-5822.2011.01664.x SummaryThe lipopeptide surfactin secreted by plant‐beneficial bacilli has crucial biological functions among which the ability to stimulate immune‐related responses in host tissues. This phenomenon is important for biological control of plant diseases but its molecular basis is still poorly understood. In this work, we used various approaches to study the mechanism governing the perception of this biosurfactant at the plant cell surface. Combining data on oxidative burst induction in tobacco cells, structure/activity relationship, competitive inhibition, insertion kinetics within plant membranes and thermodynamic determination of binding parameters on model membranes globally indicates that surfactin perception relies on a lipid‐driven process at the plasma membrane level. Such a sen... Cellular Microbiology journals http://www.medworm.com/rss/comments.php?id=5218240 Fri, 12 Aug 2011 04:00:00 +0100 5218240 http://www.medworm.com/index.php?rid=5204892&cid=s_32061_77_f&fid=32061&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1462-5822.2011.01661.x SummaryThe vascular endothelium of the blood–brain barrier (BBB) is regarded as a part of the neurovascular unit (NVU). This emerging NVU concept emphasizes the need for homeostatic signalling among the neuronal, glial and vascular endothelial cellular compartments in maintaining normal brain function. Conversely, dysfunction in any component of the NVU affects another, thus contributing to disease. Brain endothelial activation and dysfunction is observed in various neurological diseases, such as (ischemic) stroke, seizure, brain inflammation and infectious diseases and likely contributes to or exacerbates neurological conditions. The role and impact of brain endothelial factors on astroglial and neuronal activation is unclear. Similarly, it is not clear which stages of BBB endothelial a... Cellular Microbiology journals http://www.medworm.com/rss/comments.php?id=5204892 Tue, 09 Aug 2011 04:00:00 +0100 5204892 http://www.medworm.com/index.php?rid=5117865&cid=s_32061_77_f&fid=32061&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1462-5822.2011.01661.x AbstractThe vascular endothelium of the blood brain barrier (BBB) is regarded as a part of the neurovascular unit (NVU). This emerging NVU concept emphasizes the need for homeostatic signaling among the neuronal, glial, and vascular endothelial cellular compartments in maintaining normal brain function. Conversely, dysfunction in any component of the NVU affects another, thus contributing to disease. Brain endothelial activation and dysfunction is observed in various neurological diseases, such as (ischemic) stroke, seizure, brain inflammation and infectious diseases and likely contributes to or exacerbates neurological conditions. The role and impact of brain endothelial factors on astroglial and neuronal activation is unclear. Similarly, it is not clear which stages of BBB endothelial ac... Cellular Microbiology journals http://www.medworm.com/rss/comments.php?id=5117865 Mon, 08 Aug 2011 23:00:00 +0100 5117865 http://www.medworm.com/index.php?rid=5117864&cid=s_32061_77_f&fid=32061&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1462-5822.2011.01662.x SummaryIn unicellular amoebae, such as Dictyostelium discoideum, bacterial phagocytosis is a food hunting device, while in higher organisms it is the first defence barrier against microbial infection. In both cases, pathogenic bacteria exploit phagocytosis to enter the cell and multiply intracellularly. Salmonella typhimurium, the agent of food‐borne gastroenteritis, is phagocytosed by both macrophages and Dictyostelium cells. By using cell biological assays and global transcriptional analysis with DNA microarrays covering the Dictyostelium genome, we show here that S. typhimurium is pathogenic for Dictyostelium cells. Depending on the degree of virulence, which in turn depended on bacterial growth conditions, Salmonella could kill Dictyostelium cells or inhibit their growth and developm... Cellular Microbiology journals http://www.medworm.com/rss/comments.php?id=5117864 Mon, 08 Aug 2011 23:00:00 +0100 5117864 http://www.medworm.com/index.php?rid=5106232&cid=s_32061_77_f&fid=32061&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1462-5822.2011.01642.x SummaryChlamydiae are obligate intracellular Gram‐negative bacteria that cause widespread diseases in humans. Due to the intimate association between bacterium and host, Chlamydia evolved various strategies to protect their host cell against death‐inducing stimuli, allowing the bacterium to complete its development cycle. An RNA interference (RNAi)‐based screen was used to identify host cell factors required for apoptosis resistance of human epithelial cells infected with Chlamydia trachomatis serovar L2. Among the 32 validated hits, the anti‐apoptotic Bcl‐2 family member Mcl‐1 was identified as a target. Protein network analyses implicated the transcription factor hypoxia‐induced factor 1 alpha (HIF‐1α) to be central to the regulation of many of the identified targets. Fu... Cellular Microbiology journals http://www.medworm.com/rss/comments.php?id=5106232 Sun, 07 Aug 2011 23:00:00 +0100 5106232 http://www.medworm.com/index.php?rid=5156632&cid=s_32061_77_f&fid=32061&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1462-5822.2011.01658.x SummaryLeishmania parasites are well adapted to initiate infection, resist the onslaught of innate immunity and achieve a state of long‐lived persistence. In recent years, the tools available to study these interactions have developed enormously and have become much more widely available. Confocal microscopy, live cell imaging, whole animal imaging and intra‐vital 2‐photon now complement and extend the classical light and electron microscopical techniques. Coupled with approaches to generate transgenic parasites that express imaging friendly reporter proteins, these tools are making the full breadth of the life cycle accessible to imaging studies. New insights into the life history of these highly successful parasites are emerging with increasing frequency, and often with startling c... Cellular Microbiology journals http://www.medworm.com/rss/comments.php?id=5156632 Thu, 04 Aug 2011 23:00:00 +0100 5156632 http://www.medworm.com/index.php?rid=5103036&cid=s_32061_77_f&fid=32061&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1462-5822.2011.01655.x SummaryAnabaena sp. PCC 7120 is a prototype filamentous nitrogen fixing cyanobacterium, in which nitrogen fixation and photosynthesis are spatially separated. Recent molecular and cellular studies have established the importance of molecular exchange between cells in the filament, but the routes involved are still under investigation. Two current models propose either a continuous periplasm or direct connections between adjacent cells whose integrity requires the protein SepJ. We used electron tomography to analyze the ultra‐structure of the septum between vegetative cells in the Anabaena filament and were able to visualize intercellular connections that we term “SEPTOSOMES”. We observed that, whereas the existence of the septosome does not depend on the presence of SepJ, the spacing... Cellular Microbiology journals http://www.medworm.com/rss/comments.php?id=5103036 Thu, 04 Aug 2011 23:00:00 +0100 5103036 http://www.medworm.com/index.php?rid=5103035&cid=s_32061_77_f&fid=32061&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1462-5822.2011.01656.x SummaryThe early transcribed membrane proteins (ETRAMPs) are a family of small, highly charged transmembrane proteins unique to malaria parasites. Some members of the ETRAMP family have been localized to the parasitophorous vacuole membrane that separates the intracellular parasite from the host cell and thus presumably have a role in host‐parasite interactions. Although it was previously shown that two ETRAMPs are critical for rodent parasite liver stage development, the importance of most ETRAMPs during the parasite life cycle remains unknown. Here, we comprehensively identify nine new etramps in the genome of the rodent malaria parasite P. yoelii, and elucidate their conservation in other malaria parasites. etramp expression profiles are diverse throughout the parasite life cycle as m... Cellular Microbiology journals http://www.medworm.com/rss/comments.php?id=5103035 Thu, 04 Aug 2011 23:00:00 +0100 5103035 http://www.medworm.com/index.php?rid=5103034&cid=s_32061_77_f&fid=32061&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1462-5822.2011.01659.x SummaryFungal and oomycete pathogens cause many destructive diseases of plants and important diseases of humans and other animals. Fungal and oomycete plant pathogens secrete numerous effector proteins that can enter inside host cells to condition susceptibility. Until recently it has been unknown if these effectors enter via pathogen‐encoded translocons or via pathogen‐independent mechanisms. Here we review recent evidence that many fungal and oomycete effectors enter via receptor‐mediated endocytosis, and can do so in the absence of the pathogen. Surprisingly, a large number of these effectors utilize cell surface phosphatidyinositol‐3‐phosphate (PI‐3‐P) as a receptor, a molecule previously known only inside cells. Binding of effectors to PI‐3‐P appears to be mediated b... Cellular Microbiology journals http://www.medworm.com/rss/comments.php?id=5103034 Thu, 04 Aug 2011 23:00:00 +0100 5103034 http://www.medworm.com/index.php?rid=5103033&cid=s_32061_77_f&fid=32061&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1462-5822.2011.01658.x (Source: Cellular Microbiology) Cellular Microbiology journals http://www.medworm.com/rss/comments.php?id=5103033 Thu, 04 Aug 2011 23:00:00 +0100 5103033 http://www.medworm.com/index.php?rid=5094693&cid=s_32061_77_f&fid=32061&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1462-5822.2011.01640.x SummaryEnteropathogenic and enterohaemorrhagic Escherichia coli (EPEC and EHEC respectively) are attaching and effacing bacterial pathogens that cause devastating diarrhoeal disease worldwide. These pathogens depend on a type III secretion system, which functions as a molecular syringe to translocate bacterial effector proteins directly into infected host cells. One of these effectors, NleC, was recently described as a zinc metalloprotease that targets NF‐κB Rel‐A (p65) and thus contributes to dampening of inflammatory signalling during EPEC and EHEC infection. We have identified the acetyltransferase p300 as an additional target of NleC. Several biochemical techniques were employed to demonstrate specific binding of p300 by NleC. We also show that NleC causes decreased abundance of p... Cellular Microbiology journals http://www.medworm.com/rss/comments.php?id=5094693 Wed, 03 Aug 2011 23:00:00 +0100 5094693 http://www.medworm.com/index.php?rid=5138011&cid=s_32061_77_f&fid=32061&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1462-5822.2011.01666.x In this study we found that EspT induces expression of the pro‐inflammatory mediators cyclooxygenase‐2 (COX‐2) an enzyme involved in production of prostaglandin E(2) (PGE2), interleukin (Il)‐8 and Il‐1β in U937 human macrophages by activating the nuclear factor kappa‐B(NF‐κB), the extracellular signal‐regulated kinases 1 and 2 (Erk1/2), and c‐Jun N‐terminal kinase (JNK) pathways. Since EspT modulates the activation of Cdc42 and Rac1, which mediates bacterial invasion into epithelial cells, we investigated the involvement of these Rho GTPases and bacterial invasion on pro‐inflammatory responses and found that (i) Rac1, but not Cdc42, is involved in EspT‐induced Il‐8 and Il‐1β secretion and (ii) cytochalasin D inhibits EspT‐induced EPEC invasion into U937 but... Cellular Microbiology journals http://www.medworm.com/rss/comments.php?id=5138011 Sun, 31 Jul 2011 23:00:00 +0100 5138011 http://www.medworm.com/index.php?rid=5124690&cid=s_32061_77_f&fid=32061&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1462-5822.2011.01664.x SUMMARYThe lipopeptide surfactin secreted by plant‐beneficial Bacilli has crucial biological functions among which the ability to stimulate immune‐related responses in host tissues. This phenomenon is important for biological control of plant diseases but its molecular basis is still poorly understood. In this work, we used various approaches to study the mechanism governing the perception of this biosurfactant at the plant cell surface. Combining data on oxidative burst induction in tobacco cells, structure/activity relationship, competitive inhibition, insertion kinetics within plant membranes and thermodynamic determination of binding parameters on model membranes globally indicates that surfactin perception relies on a lipid‐driven process at the plasma membrane level. Such a sen... Cellular Microbiology journals http://www.medworm.com/rss/comments.php?id=5124690 Sun, 31 Jul 2011 23:00:00 +0100 5124690 http://www.medworm.com/index.php?rid=5117863&cid=s_32061_77_f&fid=32061&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1462-5822.2011.01663.x SUMMARYThe facultative intracellular pathogen Salmonella enterica serovar Typhimurium establishes a replicative niche, the Salmonella‐containing vacuole (SCV), in host cells. Here we demonstrate that these bacteria exploit the function of Arl8B, an Arf family GTPase, during infection. Following infection, Arl8B localized to SCVs and to tubulated endosomes that extended along microtubules in the host cell cytoplasm. Arl8B+ tubules partially colocalized with LAMP1 and SCAMP3. Formation of LAMP1+ tubules (the Salmonella‐induced filaments phenotype; SIFs) required Arl8B expression. SIFs formation is known to require the activity of kinesin‐1. Here we find that Arl8B is required for kinesin‐1 recruitment to SCVs. We have previously shown that SCVs undergo centrifugal movement to the cel... Cellular Microbiology journals http://www.medworm.com/rss/comments.php?id=5117863 Sun, 31 Jul 2011 23:00:00 +0100 5117863 http://www.medworm.com/index.php?rid=5103032&cid=s_32061_77_f&fid=32061&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1462-5822.2011.01660.x SummaryLeptospira interrogans is a spirochete responsible for a zoonotic disease known as leptospirosis. Leptospires are able to penetrate the abraded skin and mucous membranes and rapidly disseminate to target organs such as the liver, lungs and kidneys. How this pathogen escape from innate immune cells and spread to target organs remains poorly understood. In this paper, the intracellular trafficking undertaken by non‐pathogenic Leptospira biflexa and pathogenic L. interrogans in mouse bone marrow‐derived macrophages (BMMs) was compared. The delayed in the clearance of L. interrogans was observed. Furthermore, the acquisition of lysosomal markers by L. interrogans‐containing phagosomes lagged behind that of L. biflexa‐containing phagosomes, and although BMMs could degrade L. bifl... Cellular Microbiology journals http://www.medworm.com/rss/comments.php?id=5103032 Sun, 31 Jul 2011 23:00:00 +0100 5103032 http://www.medworm.com/index.php?rid=5076850&cid=s_32061_77_f&fid=32061&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1462-5822.2011.01657.x AbstractThe liver stage of the Plasmodium parasite remains one of the most promising targets for intervention against malaria as it is clinically silent, precedes the symptomatic blood stage and represents a bottleneck in the parasite life cycle. However, many aspects of the development of the parasite during this stage are far from understood. During the liver stage, the parasite undergoes extensive replication, forming tens of thousands of infectious merozoites from each invading sporozoite. This implies a very efficient and accurate process of cytokinesis and thus also of organelle development and segregation. We have generated for the first time Plasmodium berghei double‐fluorescent parasite lines, allowing visualisation of the apicoplast, mitochondria and nuclei in live liver stage ... Cellular Microbiology journals http://www.medworm.com/rss/comments.php?id=5076850 Sat, 30 Jul 2011 02:58:14 +0100 5076850 http://www.medworm.com/index.php?rid=5076851&cid=s_32061_77_f&fid=32061&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1462-5822.2011.01641.x SummaryThe Legionella virulence factor Mip (macrophage infectivity potentiator) contributes to bacterial dissemination within infected lung tissue. The Mip protein, which belongs to the enzyme family of FK506‐binding proteins (FKBP), binds specifically to collagen IV. We identified a surface‐exposed Mip‐binding sequence in the NC1 domain of human collagen IV α1. The corresponding collagen IV‐derived peptide (P290) co‐precipitated with Mip and competitively inhibited the Mip–collagen IV binding. Transmigration of Legionella pneumophila across a barrier of NCI‐H292 lung epithelial cells and extracellular matrix was efficiently inhibited by P290. This significantly reduced transmigration was comparable to the inefficient transmigration of PPIase‐negative Mip mutant or rapamyc... Cellular Microbiology journals http://www.medworm.com/rss/comments.php?id=5076851 Wed, 27 Jul 2011 23:00:00 +0100 5076851 http://www.medworm.com/index.php?rid=5061659&cid=s_32061_77_f&fid=32061&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1462-5822.2011.01654.x SummaryTetanus and botulinum neurotoxins are di‐chain proteins that cause paralysis by inhibiting neuroexocytosis. These neurotoxins enter into nerve terminals via endocytosis inside synaptic vesicles, whose acidic pH induces a structural change of the neurotoxin molecule that becomes capable of translocating its L chain into the cytosol, via a transmembrane protein‐conducting channel made by the H chain. This is the least understood step of the intoxication process primarily because it takes place inside vesicles within the cytosol. In the present study, we describe how this passage was made accessible to investigation by making it to occur at the surface of neurons. The neurotoxin, bound to the plasma membrane in the cold, was exposed to a warm low pH extracellular medium and the ent... Cellular Microbiology journals http://www.medworm.com/rss/comments.php?id=5061659 Mon, 25 Jul 2011 20:08:21 +0100 5061659 http://www.medworm.com/index.php?rid=5156633&cid=s_32061_77_f&fid=32061&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1462-5822.2011.01654.x SummaryTetanus and botulinum neurotoxins are di‐chain proteins that cause paralysis by inhibiting neuroexocytosis. These neurotoxins enter into nerve terminals via endocytosis inside synaptic vesicles, whose acidic pH induces a structural change of the neurotoxin molecule that becomes capable of translocating its L chain into the cytosol, via a transmembrane protein‐conducting channel made by the H chain. This is the least understood step of the intoxication process primarily because it takes place inside vesicles within the cytosol. In the present study, we describe how this passage was made accessible to investigation by making it to occur at the surface of neurons. The neurotoxin, bound to the plasma membrane in the cold, was exposed to a warm low pH extracellular medium and the ent... Cellular Microbiology journals http://www.medworm.com/rss/comments.php?id=5156633 Sun, 24 Jul 2011 23:00:00 +0100 5156633 http://www.medworm.com/index.php?rid=5124692&cid=s_32061_77_f&fid=32061&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1462-5822.2011.01644.x SummaryMacrophages have been shown to kill Mycobacterium tuberculosis through the action of the antimicrobial peptide cathelicidin (CAMP), whose expression was shown to be induced by 1,25‐dihydroxyvitamin D3 (1,25D3). Here, we investigated in detail the antimycobacterial effect of murine and human cathelicidin against Mycobacterium smegmatis and M. bovis BCG infections. We have synthesized novel LL‐37 peptide variants that exhibited potent in vitro bactericidal activity against M. smegmatis, M. bovis BCG and M. tuberculosis H37Rv, as compared with parental peptide. We show that the exogenous addition of LL‐37 or endogenous overexpression of cathelicidin in macrophages significantly reduced the intracellular survival of mycobacteria relative to control cells. An upregulation o... Cellular Microbiology journals http://www.medworm.com/rss/comments.php?id=5124692 Sun, 24 Jul 2011 23:00:00 +0100 5124692 http://www.medworm.com/index.php?rid=5124691&cid=s_32061_77_f&fid=32061&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1462-5822.2011.01650.x SummaryThe type 1 fimbriae of uropathogenic Escherichia coli (UPEC) have been described as important for the establishment of bladder infections and urinary tract infections (UTI). Urinary prostaglandin (PG) levels and cyclooxygenase (COX)‐2 expression in urine particulates may increase with infectious and inflammatory processes, including UTIs. We investigated the mechanisms underlying the modulation of COX‐2 expression through the invasion of type 1 fimbriated UPEC strain J96 (J96‐1) in human bladder 5637 cells. Bladder 5637 cells infected with J96‐1 induced increases in the expression of COX‐2 and secretion of PGE2. By using specific inhibitors and short hairpin RNA (shRNA), we have demonstrated that the activation of extracellular signal‐related kinase (ERK), c‐Jun‐NH2�... Cellular Microbiology journals http://www.medworm.com/rss/comments.php?id=5124691 Sun, 24 Jul 2011 23:00:00 +0100 5124691 http://www.medworm.com/index.php?rid=5061669&cid=s_32061_77_f&fid=32061&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1462-5822.2011.01644.x SummaryMacrophages have been shown to kill Mycobacterium tuberculosis through the action of the antimicrobial peptide cathelicidin (CAMP), whose expression was shown to be induced by 1,25‐dihydroxyvitamin D3 (1,25D3). Here, we investigated in detail the anti‐mycobacterial effect of murine and human cathelicidin against M. smegmatis and M. bovis‐BCG infections. We have synthesized novel LL‐37 peptide variants that exhibited potent in vitro bactericidal activity against M. smegmatis, M. bovis BCG and M. tuberculosis H37Rv, as compared to parental peptide. We show that the exogenous addition of LL‐37 or endogenous over‐expression of cathelicidin in macrophages significantly reduced the intracellular survival of mycobacteria relative to control cells. An up‐regulation of cathelic... Cellular Microbiology journals http://www.medworm.com/rss/comments.php?id=5061669 Sun, 24 Jul 2011 23:00:00 +0100 5061669 http://www.medworm.com/index.php?rid=5061668&cid=s_32061_77_f&fid=32061&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1462-5822.2011.01645.x SUMMARYThe ability of enteric pathogens to perceive and adapt to distinct environments within the metazoan intestinal tract is critical for pathogenesis, however the preponderance of interactions between microbe‐ and host‐derived factors remain to be fully understood. Salmonella enterica serovar Typhimurium is a medically important enteric bacterium that colonizes, proliferates, and persists in the intestinal lumen of the nematode Caenorhabditis elegans. Several Salmonella virulence factors important in murine and tissue culture models also contribute to worm mortality and intestinal persistence. For example, PhoP and the virulence plasmid pSLT are virulence factors required for resistance to the C. elegans antimicrobial peptide SPP‐1. To uncover additional determinants required for ... Cellular Microbiology journals http://www.medworm.com/rss/comments.php?id=5061668 Sun, 24 Jul 2011 23:00:00 +0100 5061668 http://www.medworm.com/index.php?rid=5061667&cid=s_32061_77_f&fid=32061&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1462-5822.2011.01646.x AbstractDefense mechanisms against intracellular bacterial pathogens are incompletely understood. Our study characterizes a type I IFN‐dependent cell‐autonomous defense pathway directed against Legionella pneumophila, an intracellular model organism and frequent cause of pneumonia. We show that macrophages infected with L. pneumophila produced IFNβ in a STING‐ and IRF3‐dependent manner. Paracrine type I IFNs stimulated up‐regulation of IFN‐stimulated genes and a cell‐autonomous defense pathway acting on replicating and non‐replicating Legionella within their specialized vacuole. Our infection experiments in mice lacking receptors for type I and/or II IFNs show that type I IFNs contribute to expression of IFN‐stimulated genes and to bacterial clearance as well as resistan... Cellular Microbiology journals http://www.medworm.com/rss/comments.php?id=5061667 Sun, 24 Jul 2011 23:00:00 +0100 5061667 http://www.medworm.com/index.php?rid=5061666&cid=s_32061_77_f&fid=32061&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1462-5822.2011.01647.x We report an adhesion‐dependent disorganization of the apical F‐actin cytoskeleton that, in turn, results in a dramatic loss of distribution of functional brush border‐associated proteins, including sucrase‐isomaltase (SI), dipeptidylpeptidase IV (DPP IV) and fructose transporter, GLUT5, and a decrease in sucrose enzyme activity in G. intestinalis‐infected enterocyte‐like cells. We observed that the G. intestinalis trophozoite promotes an adhesion‐dependent decrease in transepithelial resistance (TER) accompanied by a rearrangement of functional tight junction (TJ)‐associated occludin, and delocalization of claudin‐1. Finally, we found that whereas the occludin rearrangement induced by G. intestinalis was related to apical F‐actin disorganization, the delocalization of ... Cellular Microbiology journals http://www.medworm.com/rss/comments.php?id=5061666 Sun, 24 Jul 2011 23:00:00 +0100 5061666 http://www.medworm.com/index.php?rid=5061665&cid=s_32061_77_f&fid=32061&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1462-5822.2011.01648.x SummaryPlasmodium falciparum malaria is an intracellular parasite that is transmitted by Anopheles mosquitoes. It is responsible for approximately 1 million deaths per year. Most deaths occur as a result of complications such as severe anemia or cerebral malaria (coma). The complement receptor 1 is a key complement regulator found on the surface of red cells and most leukocytes. A growing body of evidence suggests that this molecule plays a critical role in the pathogenesis of P. falciparum malaria. Initial reports showed that CR1 enables the binding of infected red cells to uninfected red cells to form rosettes which can potentially obstruct small capillaries. However, further evidence suggests that CR1 is also important in the control of complement activation and immune complex formation... Cellular Microbiology journals http://www.medworm.com/rss/comments.php?id=5061665 Sun, 24 Jul 2011 23:00:00 +0100 5061665 http://www.medworm.com/index.php?rid=5061664&cid=s_32061_77_f&fid=32061&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1462-5822.2011.01649.x AbstractWest Nile virus (WNV), from the Flaviviridae family, is a re‐emerging zoonotic pathogen of medical importance. In humans, WNV infection may cause life‐threatening meningoencephalitis or long‐term neurologic sequelae. WNV is transmitted by Culex spp mosquitoes and both the arthropod vector and the mammalian host are equipped with antiviral innate immune mechanisms sharing a common phylogeny. As far as the current evidence is able to demonstrate, mosquitoes primarily rely on RNA interference, Toll, Imd and JAK‐STAT signaling pathways for limiting viral infection, while mammals are provided with these and other more complex antiviral mechanisms involving antiviral effectors, inflammatory mediators, and cellular responses triggered by highly specialized pathogen detection mecha... Cellular Microbiology journals http://www.medworm.com/rss/comments.php?id=5061664 Sun, 24 Jul 2011 23:00:00 +0100 5061664 http://www.medworm.com/index.php?rid=5061663&cid=s_32061_77_f&fid=32061&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1462-5822.2011.01650.x AbstractThe type 1 fimbriae of uropathogenic Escherichia coli (UPEC) have been described as important for the establishment of bladder infections and urinary tract infections (UTI). Urinary prostaglandin (PG) levels and cyclooxygenase (COX)‐2 expression in urine particulates may increase with infectious and inflammatory processes, including UTIs. We investigated the mechanisms underlying the modulation of COX‐2 expression through the invasion of type 1 fimbriated UPEC strain J96 (J96‐1) in human bladder 5637 cells. Bladder 5637 cells infected with J96‐1 induced increases in the expression of COX‐2 and secretion of PGE2. By using specific inhibitors and short hairpin RNA (shRNA), we have demonstrated that the activation of extracellular signal‐related kinase (ERK), c‐Jun‐NH2... Cellular Microbiology journals http://www.medworm.com/rss/comments.php?id=5061663 Sun, 24 Jul 2011 23:00:00 +0100 5061663 http://www.medworm.com/index.php?rid=5061662&cid=s_32061_77_f&fid=32061&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1462-5822.2011.01652.x SummaryMale gametogenesis occurs directly after uptake of malaria parasites by the mosquito vector and leads to the release of eight nucleated flagellar gametes. Here, we report that one of the two parasite actin isoforms, named actin II, is essential for this process. Disruption of actin II in Plasmodium berghei resulted in viable asexual blood stages, but male gametogenesis was specifically inhibited. Upon activation, male gametocyte DNA was replicated normally and axonemes assembled, but egress from the host cell was inhibited, and axoneme motility abolished. The major actin isoform, actin I, displayed dual localization to the cytoplasm and the nucleus in male gametocytes. After activation actin I was found to be restricted to the cytoplasm. In actII(‐) mutant parasites, this re‐loc... Cellular Microbiology journals http://www.medworm.com/rss/comments.php?id=5061662 Sun, 24 Jul 2011 23:00:00 +0100 5061662 http://www.medworm.com/index.php?rid=5061661&cid=s_32061_77_f&fid=32061&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1462-5822.2011.01651.x SUMMARYInvasion of non‐phagocytic cells by a number of bacterial pathogens involves the subversion of the actin cytoskeletal remodelling machinery to produce actin‐rich cell surface projections designed to engulf the bacteria. The signalling that occurs to induce these actin‐rich structures has considerable overlap amongst a diverse group of bacteria. The molecular organisation within these structures act in concert to internalise the invading pathogen. This dynamic process could be subdivided into three acts ‐ actin recruitment, engulfment, and finally, actin disassembly/internalisation. This review will present the current state of knowledge of the molecular processes involved in each stage of bacterial invasion, and provide a perspective that highlights the temporal and spatial ... Cellular Microbiology journals http://www.medworm.com/rss/comments.php?id=5061661 Sun, 24 Jul 2011 23:00:00 +0100 5061661 http://www.medworm.com/index.php?rid=5061660&cid=s_32061_77_f&fid=32061&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1462-5822.2011.01653.x ABSTRACTA number of viruses transport their genomic material from cell to cell enclosed within a lipid bilayer that is in turn encased within a symmetric protein shell. This review focuses in a group of RNA viruses that have this type of virions. This group includes several of important human pathogenic viruses, such as the hepatitis C virus, dengue virus, chikungunya virus, rubella virus, and the bunyaviruses. The best studied are the flaviviruses and the alphaviruses, which have a β‐sheet rich class II viral fusion protein used for entry into susceptible cells. We extend here the class II concept to encompass symmetric viruses in which the envelope proteins are derived from a precursor polyprotein containing two transmembrane glycoproteins arranged in tandem. The first glycoprotein ac... Cellular Microbiology journals http://www.medworm.com/rss/comments.php?id=5061660 Sun, 24 Jul 2011 23:00:00 +0100 5061660 http://www.medworm.com/index.php?rid=5048858&cid=s_32061_77_f&fid=32061&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1462-5822.2011.01633.x (Source: Cellular Microbiology) Cellular Microbiology journals http://www.medworm.com/rss/comments.php?id=5048858 Fri, 22 Jul 2011 00:39:45 +0100 5048858 http://www.medworm.com/index.php?rid=5057445&cid=s_32061_77_f&fid=32061&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1462-5822.2011.01639.x SummaryThe pathogenesis of Staphylococcus aureus infective endocarditis (IE) is postulated to involve invasion and damage of endothelial cells (ECs). However, the precise relationships between S. aureus–EC interactions in vitro and IE virulence and treatment outcomes in vivo are poorly defined. Ten methicillin‐resistant S. aureus (MRSA) clinical isolates previously tested for their virulence and vancomycin responsiveness in an experimental IE model were assessed in vitro for their haemolytic activity, protease production, and capacity to invade and damage ECs. There was a significant positive correlation between the in vitro EC damage caused by these MRSA strains and their virulence during experimental IE (in terms of bacterial densities in target tissues; P < 0.02). Importa... Cellular Microbiology journals http://www.medworm.com/rss/comments.php?id=5057445 Wed, 20 Jul 2011 23:00:00 +0100 5057445 http://www.medworm.com/index.php?rid=5018548&cid=s_32061_77_f&fid=32061&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1462-5822.2011.01636.x SummaryAt the site of infection, pro‐inflammatory cytokines locally produced by macrophages infected with Trypanosoma cruzi can activate surrounding non‐professional phagocytes such as fibroblasts, epithelial and endothelial cells, which can be further invaded by the parasite. The effect of secreted soluble factors on the invasion of these cells remains, however, to be established. We show here that two epithelial cell lines become significantly susceptible to the infection by the Y strain of T. cruzi after tumour necrosis factor (TNF) treatment. The increase in the invasion was correlated with the increasing concentration of recombinant TNF added to cultures of HEK293T or LLC‐MK2 cells. Supernatants taken from PMA‐differentiated human monocytes infected with T. cruzi also incr... Cellular Microbiology journals http://www.medworm.com/rss/comments.php?id=5018548 Mon, 11 Jul 2011 23:00:00 +0100 5018548 http://www.medworm.com/index.php?rid=5018556&cid=s_32061_77_f&fid=32061&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1462-5822.2011.01637.x SummaryNon‐typhoidal Salmonella (NTS) serotypes cause a localized gastroenteritis in immunocompetent individuals. In contrast, primary immunodeficiencies that impair interleukin‐23 (IL‐23)‐dependent pathways are associated in humans with disseminated NTS bloodstream infections (bacteraemia). The recent use of animal models has helped to define the role the IL‐23 axis plays during NTS gastroenteritis, but additional work is needed to elucidate how this host defence pathway prevents NTS bacteraemia. (Source: Cellular Microbiology) Cellular Microbiology journals http://www.medworm.com/rss/comments.php?id=5018556 Sun, 10 Jul 2011 23:00:00 +0100 5018556 http://www.medworm.com/index.php?rid=5018555&cid=s_32061_77_f&fid=32061&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1462-5822.2011.01625.x SummaryInduction of necrotic death in macrophages is a primary virulence determinant of Mycobacterium tuberculosis. The ESX‐1 secretion system and its substrate ESAT‐6 are required for M. tuberculosis to induce necrosis, but host factors that mediate the ESAT‐6‐promoted necrosis remain unknown. Here we report that ESAT‐6‐promoted necrotic death in THP‐1 human macrophages is dependent on the NLRP3 inflammasome, as shown by RNA interference and pharmacological inhibitions. Phagosomes containing ESAT‐6‐expressing M. tuberculosis recruit markers previously associated with damaged phagosomal membrane, such as galectin‐3 and ubiquitinated protein aggregates. In addition, ESAT‐6 promoted lysosomal permeabilization by M. tuberculosis. ESAT‐6 mutants defective for ubiquitina... Cellular Microbiology journals http://www.medworm.com/rss/comments.php?id=5018555 Sun, 10 Jul 2011 23:00:00 +0100 5018555 http://www.medworm.com/index.php?rid=5018554&cid=s_32061_77_f&fid=32061&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1462-5822.2011.01626.x SummaryOral tolerance is a process that allows generation of systemic unresponsiveness to food antigens. Hence if the same antigen is introduced systemically even under immunogenic conditions it does not induce immune responsiveness. Dendritic cells (DCs) have been identified as essential players in this process. DCs in the gut are located in a strategic position as they can interact directly with luminal antigens or indirectly after their transcytosis across epithelial cells. DCs can then migrate to associated lymphoid tissues to induce tolerance. Antigen presenting cells in the gut are specialized in function and have divided their labour so that there are cells capable to migrate to the draining mesenteric lymph node for induction of T regulatory cells, while other subsets are resident ... Cellular Microbiology journals http://www.medworm.com/rss/comments.php?id=5018554 Sun, 10 Jul 2011 23:00:00 +0100 5018554 http://www.medworm.com/index.php?rid=5018553&cid=s_32061_77_f&fid=32061&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1462-5822.2011.01627.x SummarySpiroplasma poulsonii and its relatives are facultative, vertically transmitted endosymbionts harboured by several Drosophila species. Their long‐term survival requires not only evasion of host immunity, but also that Spiroplasma does not have a net detrimental effect on host fitness. These requirements provide the central framework for interactions between host and endosymbiont. We use Drosophila melaogaster as a model to unravel aspects of the mechanistic basis of endosymbiont–host immune interactions. Here we show that Spiroplasma does not activate an immune response in Drosophila and is not susceptible to either the cellular or humoral arms of the Drosophila immune system. We gain unexpected insight into host factors that can promote Spiroplasma growth by showing that activa... Cellular Microbiology journals http://www.medworm.com/rss/comments.php?id=5018553 Sun, 10 Jul 2011 23:00:00 +0100 5018553 http://www.medworm.com/index.php?rid=5018552&cid=s_32061_77_f&fid=32061&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1462-5822.2011.01628.x SummaryThe ubiquitin proteasome system and autophagy constitute key signalling pathways in the host response to infection. The identification of adaptors linking the two pathways has prompted a re‐examination of the latter's involvement in inflammatory reactions and the clearance of bacteria. The ubiquitin–autophagy pathway is a preferred target for effectors from pathogens that seek to exploit and evade the host defence mechanisms. A number of new players and signalling nodes have recently been identified. Here, we discuss these new insights into the host's control of bacterial infection. (Source: Cellular Microbiology) Cellular Microbiology journals http://www.medworm.com/rss/comments.php?id=5018552 Sun, 10 Jul 2011 23:00:00 +0100 5018552 http://www.medworm.com/index.php?rid=5018551&cid=s_32061_77_f&fid=32061&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1462-5822.2011.01629.x SummaryAntigenic variation to fool the immune system is one of the molecular tricks Plasmodium uses to maintain infection in its human host. The exclusive expression of the surface‐exposed PfEMP1 molecules, encoded by var genes, is the best example for this. Central questions regarding the dynamics of antigenic variation, namely the rate of switching and the regulation of var gene expression in Plasmodium falciparum, are yet unanswered. To elucidate the in vivo situation, we studied var gene switching by analysing the var transcripts from parasites isolated from 20 non‐immune malaria patients as well as during subsequent in vitro generations. Parasites were found to be highly co‐ordinated as the whole population isolated from individual patients usually expressed only one dominant �... Cellular Microbiology journals http://www.medworm.com/rss/comments.php?id=5018551 Sun, 10 Jul 2011 23:00:00 +0100 5018551 http://www.medworm.com/index.php?rid=5018550&cid=s_32061_77_f&fid=32061&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1462-5822.2011.01630.x SummaryNucleotides are released into the extracellular milieu from infected cells and cells at inflammatory sites. The extracellular nucleotides bind to specific purinergic (P2) receptors and thereby induce a variety of cellular responses including anti‐parasitic effects. Here we investigated whether extracellular nucleotides affect leishmanial infection in macrophages, and found that UTP reduces strongly the parasite load in peritoneal macrophages. Ultrastructural analysis of infected cells revealed that UTP induced morphological damage in the intracellular parasites. Uridine nucleotides also induced dose‐dependent apoptosis of macrophages and production of ROI and RNI only in infected macrophages. The intracellular calcium measurements of infected cells showed that the response to UT... Cellular Microbiology journals http://www.medworm.com/rss/comments.php?id=5018550 Sun, 10 Jul 2011 23:00:00 +0100 5018550 http://www.medworm.com/index.php?rid=5018549&cid=s_32061_77_f&fid=32061&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1462-5822.2011.01631.x SummaryThe enteric pathogens enteropathogenic Escherichia coli (EPEC), enterohaemorrhagic E. coli (EHEC) and Shigella flexneri all translocate at least one effector protein of the EspG protein family into host cells via a type III secretion system (T3SS). The EspG family comprises EspG, EspG2 and VirA. From a Y2H screen, we identified the Golgi matrix protein GM130 as a potential binding partner of EspG. We confirmed EspG:GM130 protein interaction by affinity co‐purification. In co‐immunoprecipitation experiments EspG was co‐precipitated with GM130 while both GM130 and tubulins were co‐precipitated with EspG. When expressed ectopically in HeLa cells, the EspG protein family all localized to the Golgi and induced fragmentation of the Golgi apparatus. All EspG family proteins were al... Cellular Microbiology journals http://www.medworm.com/rss/comments.php?id=5018549 Sun, 10 Jul 2011 23:00:00 +0100 5018549 http://www.medworm.com/index.php?rid=5018557&cid=s_32061_77_f&fid=32061&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1462-5822.2011.01632.x SummaryMany bacterial pathogens rely on an intracellular cycle to ensure their proliferation within infected hosts, through their ability to avoid or circumvent host bactericidal pathways. Recent evidence supports an increasingly important role for the autophagy pathway in innate immune defences against intracellular pathogens, as a mechanism of capture of either cytosol‐adapted or vacuolar bacteria that redirect them to the lysosomal compartment for killing. Antibacterial autophagy, also referred to as xenophagy, involves selective recognition of intracellular bacteria and their targeting to the autophagic machinery for degradation. Here we review recent advances in our molecular understanding of these processes, and in how bacteria have adapted to avoid xenophagy or even take advantage... Cellular Microbiology journals http://www.medworm.com/rss/comments.php?id=5018557 Sat, 09 Jul 2011 23:00:00 +0100 5018557 http://www.medworm.com/index.php?rid=5007075&cid=s_32061_77_f&fid=32061&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1462-5822.2011.01621.x SummarySalmonella enterica deploys the giant non‐fimbrial adhesin SiiE to adhere to the apical side of polarized epithelial cells. The establishment of close contact is a prerequisite for subsequent invasion mediated by translocation of effector proteins of the Salmonella Pathogenicity Island 1 (SPI1)‐encoded type III secretion system (T3SS). Although SiiE is secreted into the culture medium, the adhesin is retained on the bacterial envelope in the phase of highest bacterial invasiveness. To dissect the structural requirements for secretion, retention and adhesive properties, comprehensive deletional and functional analyses of various domains of SiiE were performed. We observed that β‐sheet and coiled‐coil domains in the N‐terminal moiety of SiiE are required for the control of ... Cellular Microbiology journals http://www.medworm.com/rss/comments.php?id=5007075 Mon, 04 Jul 2011 23:00:00 +0100 5007075 http://www.medworm.com/index.php?rid=4997209&cid=s_32061_77_f&fid=32061&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1462-5822.2011.01634.x SummaryThe bacterial virulence factors Shiga toxins (Stxs) are expressed by Shigella dysenteriae serotype 1 and certain Escherichia coli strains. Stxs are protein synthesis inhibitors and induce apoptosis in many cell types. Stxs induce apoptosis via prolonged endoplasmic reticulum stress signalling to activate both extrinsic and intrinsic pathways in human myeloid cells. Studies have shown that autophagy, a lysosome‐dependent catabolic process, may be associated with activation of pro‐survival or death processes. It is currently unknown if autophagy contributes to apoptosis or protects cells from Stxs. To study cellular responses to Stxs, we intoxicated toxin‐sensitive cells (THP‐1 and HK‐2 cells), and toxin‐resistant cells (primary human monocyte‐derived macrophages) and ex... Cellular Microbiology journals http://www.medworm.com/rss/comments.php?id=4997209 Sat, 02 Jul 2011 23:00:00 +0100 4997209 http://www.medworm.com/index.php?rid=4992067&cid=s_32061_77_f&fid=32061&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1462-5822.2011.01623.x SummaryThe bacterial effector proteins IpgB1 and IpgB2 of Shigella and Map of Escherichia coli activate the Rho GTPases Rac1, RhoA and Cdc42, respectively, whereas YopE and YopT of Yersinia inhibit these Rho family GTPases. We established a Yersinia toolbox which allows to study the cellular effects of these effectors in different combinations in the context of Yersinia type 3 secretion system (Ysc)‐T3SS‐mediated injection into HeLa cells. For this purpose hybrid proteins were constructed by fusion of YopE with the effector protein of interest. As expected, injected hybrid proteins induced membrane ruffles and Yersinia uptake for IpgB1, stress fibres for IpgB2 and microspikes for Map. By co‐infection experiments we could demonstrate (i) IpgB2‐mediated and ROCK‐dependent inhibitio... Cellular Microbiology journals http://www.medworm.com/rss/comments.php?id=4992067 Thu, 30 Jun 2011 23:00:00 +0100 4992067 http://www.medworm.com/index.php?rid=4974999&cid=s_32061_77_f&fid=32061&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1462-5822.2011.01620.x SummarySevere malaria, including cerebral malaria (CM), is characterized by the sequestration of parasitized erythrocytes in the microvessels after cytoadherence to endothelial cells. Products of parasite origin, such as haemozoin (HZ), contribute to the pathogenesis of severe malaria by interfering with host inflammatory response. In human monocytes, HZ enhanced the levels of matrix metalloproteinase‐9 (MMP‐9), a protease involved in neuroinflammation. Here the effects of HZ on the regulation of MMPs by the human microvascular endothelial cell line HMEC‐1 were investigated. Cells treated with natural (n)HZ appeared elongated instead of polygonal, and formed microtubule‐like vessels on synthetic basement membrane. nHZ enhanced total gelatinolytic activity by inducing proMMP‐9 and... Cellular Microbiology journals http://www.medworm.com/rss/comments.php?id=4974999 Sun, 26 Jun 2011 23:00:00 +0100 4974999 http://www.medworm.com/index.php?rid=4974998&cid=s_32061_77_f&fid=32061&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1462-5822.2011.01624.x SummaryJapanese encephalitis virus (JEV), a mosquito‐borne flavivirus, causes acute encephalitis with high mortality in humans. We used a pair of virulent (RP‐9) and attenuated (RP‐2ms) variants of JEV to pull down the cell surface molecules bound with JEV particle; their identities were revealed by LC‐MS/MS analysis. One major protein bound with RP‐9 and weakly with RP‐2ms was identified as the intermediate filament protein vimentin. Infection of RP‐9 but not that of RP‐2ms was blocked by anti‐vimentin antibodies and by recombinant‐expressed vimentin proteins. Knockdown of vimentin expression reduced the levels of viral binding and viral production of RP‐9, but not that of RP‐2ms. The different vimentin dependency for JEV infection could be attributed to the major ... Cellular Microbiology journals http://www.medworm.com/rss/comments.php?id=4974998 Sun, 26 Jun 2011 23:00:00 +0100 4974998 http://www.medworm.com/index.php?rid=4975001&cid=s_32061_77_f&fid=32061&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1462-5822.2011.01618.x SummaryType IV secretion systems (T4SS) are specialized protein complexes used by many bacterial pathogens for the delivery of effector molecules that subvert varied host cellular processes. Brucella spp. are facultative intracellular pathogens capable of survival and replication inside mammalian cells. Brucella T4SS (VirB) is essential to subvert lysosome fusion and to create an organelle permissive for replication. One possible role for VirB is to translocate effector proteins that modulate host cellular functions for the biogenesis of the replicative organelle. We hypothesized that proteins with eukaryotic domains or protein–protein interaction domains, among others, would be good candidates for modulation of host cell functions. To identify these candidates, we performed an in silico... Cellular Microbiology journals http://www.medworm.com/rss/comments.php?id=4975001 Thu, 23 Jun 2011 23:00:00 +0100 4975001 http://www.medworm.com/index.php?rid=4975000&cid=s_32061_77_f&fid=32061&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1462-5822.2011.01619.x SummaryCyclic‐di‐GMP (c‐di‐GMP) regulates many important bacterial processes. Freely diffusible intracellular c‐di‐GMP is determined by the action of metabolizing enzymes that allow integration of numerous input signals. c‐di‐GMP specifically regulates multiple cellular processes by binding to diverse target molecules. This review highlights important questions in research into the mechanisms of c‐di‐GMP signalling and its role in bacterial physiology. (Source: Cellular Microbiology) Cellular Microbiology journals http://www.medworm.com/rss/comments.php?id=4975000 Thu, 23 Jun 2011 23:00:00 +0100 4975000 http://www.medworm.com/index.php?rid=4975003&cid=s_32061_77_f&fid=32061&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1462-5822.2011.01622.x SummaryIncreased numbers of T regulatory cells (Tregs), key mediators of immune homeostasis, were reported in human and murine malaria and it is current opinion that these cells play a role in balancing protective immunity and pathogenesis during infection. However, the mechanisms governing their expansion during malaria infection are not completely defined. In this article we show that soluble extracts of Plasmodium falciparum (PfSEs), but not equivalent preparation of uninfected erythrocytes, induce the differentiation of polyclonally activated CD4+ cells in Tregs endowed with strong suppressive activity. PfSEs activate latent TGFβ bound on the membrane of Treg cells, thus allowing the cytokine interaction with TGFβ receptor, and inducing Foxp3 gene expression and TGFβ production. The... Cellular Microbiology journals http://www.medworm.com/rss/comments.php?id=4975003 Wed, 22 Jun 2011 23:00:00 +0100 4975003 http://www.medworm.com/index.php?rid=4932881&cid=s_32061_77_f&fid=32061&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1462-5822.2011.01616.x (Source: Cellular Microbiology) Cellular Microbiology journals http://www.medworm.com/rss/comments.php?id=4932881 Thu, 16 Jun 2011 22:41:51 +0100 4932881 http://www.medworm.com/index.php?rid=4932880&cid=s_32061_77_f&fid=32061&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1462-5822.2011.01635.x SummaryCoiled‐coil domains in eukaryotic and prokaryotic proteins contribute to diverse structural and regulatory functions. Here we have used in silico analysis to predict which proteins in the proteome of the enteric pathogen, Salmonellaenterica serovar Typhimurium, harbor coiled‐coil domains. We found that coiled‐coil domains are especially prevalent in virulence‐associated proteins, including type III effectors. Using SopB as a model coiled‐coil domain type III effector, we have investigated the role of this motif in various aspects of effector function including chaperone binding, secretion and translocation, protein stability, localization and biological activity. Compared to wild type SopB, SopB coiled‐coil mutants were unstable, both inside bacteria and after translocat... Cellular Microbiology journals http://www.medworm.com/rss/comments.php?id=4932880 Thu, 16 Jun 2011 22:41:44 +0100 4932880 http://www.medworm.com/index.php?rid=4920463&cid=s_32061_77_f&fid=32061&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1462-5822.2011.01615.x SummaryBacterial and parasitic intracellular pathogens or their secreted products have been shown to induce host cell transcriptional responses, which may benefit the host, favour the microorganism or be unrelated to the infection. In most instances, however, it is not known if the host cell nucleus is proximately required for the development of an intracellular infection. This information can be obtained by the infection of artificially enucleated host cells (cytoplasts). This model, although rather extensively used in studies of viral infection, has only been applied to few bacterial pathogens, which do not include Mycobacterium spp. Here, we investigate the internalization, phagosome biogenesis and survival of M. smegmatis in enucleated type II alveolar epithelial cells. Cytoplasts were... Cellular Microbiology journals http://www.medworm.com/rss/comments.php?id=4920463 Wed, 08 Jun 2011 23:00:00 +0100 4920463 http://www.medworm.com/index.php?rid=4891909&cid=s_32061_77_f&fid=32061&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1462-5822.2011.01609.x SummaryOptimizing the development of modern molecular vaccines requires a complex series of interdisciplinary efforts involving basic scientists, immunologists, molecular biologists, clinical vaccinologists, bioinformaticians and epidemiologists. This review summarizes some of the major issues that must be carefully considered. The intent of the authors is to briefly describe key components of the development process to give the reader an overview of the challenges faced from vaccine concept to vaccine delivery. Every vaccine requires unique features based on the biology of the pathogen, the nature of the disease and the target population for vaccination. This review presents general concepts relevant for the design and development of ideal vaccines protective against diverse pathogens. (S... Cellular Microbiology journals http://www.medworm.com/rss/comments.php?id=4891909 Wed, 01 Jun 2011 23:00:00 +0100 4891909 http://www.medworm.com/index.php?rid=4882881&cid=s_32061_77_f&fid=32061&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1462-5822.2011.01602.x SummaryThe parasitic protozoan Leishmania is the etiological agent of human leishmaniasis worldwide. It undergoes cellular differentiation from the sandfly promastigote form into amastigotes within mammalian macrophages, a process that is essential for its intracellular survival. Here, we characterized the Leishmania infantum PERK eIF2alpha kinase homologue and addressed its role in the parasite's cytodifferentiation. We show that Leishmania PERK is an endoplasmic reticulum (ER) transmembrane protein that largely colocalizes with the ER BiP chaperone. The Leishmania PERK catalytic kinase domain undergoes autohyperphosphorylation and phosphorylates the translation initiation factor 2‐alpha subunit (eIF2alpha) in vitro at threonine 166. We also report that PERK is post‐translationally re... Cellular Microbiology journals http://www.medworm.com/rss/comments.php?id=4882881 Sun, 29 May 2011 23:00:00 +0100 4882881