B B Finlay

..In this review, we highlight and compare some of the many molecular mechanisms that bacterial and viral pathogens use to evade host immune defenses...

..The present study shows that virulence genes associated epidemiologically with outbreaks and HUS after non-O157 STEC infection are pivotal to the initiation, progression, and outcome of in vivo disease...

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..Due to the critical role of phoP in Salmonella virulence, further studies in this area will likely reveal aspects of the interaction between Salmonella and bile that are relevant to disease...

..Many TLRs utilize a common signalling pathway that relies on activation of the kinase IRAK4 and the transcription factor NFkappaB for the rapid expression of immunity genes...

..For this pathogen, no appropriate model has been reported in which to examine infection kinetics and natural dissemination to the brain...

..Collectively, these examples represent many key microbial virulence mechanisms that have led to a much deeper understanding of both microbial pathogens and GTPase functions...

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..Therefore, to facilitate patient care and improve outcomes, it is important to understand the T3SS-mediated virulence processes and to target T3SSs in therapeutic and prophylactic development efforts...

..rodentium infection of highly susceptible mouse strains. Determining the basis for these strains' susceptibility to intestinal colonization by an A/E pathogen will be the focus of future studies...

..The findings of this study together provide the first evidence that EspZ localizes to host mitochondria and that TIM17b contributes to protection against rapid cell death during EPEC infection...

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..Recently, the molecular mechanisms of such antiphagocytic properties have been elucidated for some pathogens. Such mechanisms illustrate the diversity of mechanisms bacterial pathogens use to avoid phagocytic uptake...

..These findings highlight some of the differences and similarities between EHEC and EPEC virulence mechanisms, which can be exploited to further define the molecular basis of pedestal formation...

..These findings highlight differences in the mechanisms of pedestal formation by these closely related pathogens and indicate that EPEC and EHEC modulate different signalling pathways to affect the host actin cytoskeleton...

..Together these various bacterial molecules contribute to the intimate relationship that is formed by EPEC with host epithelial cells which results in A/E lesion formation and diarrhea...

..Our results indicate that the LEE has been acquired by C. rodentium and A/E E. coli strains independently during evolution...

..Our findings demonstrate that Sif formation involves fusion of late endocytic compartments with the Salmonella-containing vacuole, and suggest that SifA modulates this event...

..This constitutes a novel mechanism of phagocytosis avoidance by an extracellular pathogen...

..SigD is also the first bacterial effector to be identified as an activator of Akt...

..These virulence factors often mimic host molecules, and mediate events as diverse as bacterial invasion, antiphagocytosis, and intracellular parastism...

..001). We concluded that REPEC O103 does not promote apoptosis. Furthermore, we cannot rule out the possibility that REPEC O103, in fact, decreases apoptotic levels in the rabbit ileum...

..A family of SifA-related proteins and their importance to Salmonella pathogenesis is also discussed...

..Isothermal titration calorimetry studies of Tir-CesT and enzymatic activity profiles of SigD-SigE indicate that the effector proteins are not globally unfolded in the presence of their cognate chaperones...

..egr-1 is also induced during infection of mice by the A/E pathogen Citrobacter rodentium, suggesting that both Egr-1 and the activation of this mitogen-activated protein kinase signal transduction pathway may play a role in disease...

..Together these developments may lead to new therapeutic strategies...

..Inhibition of pedestal formation by tyrosine kinase inhibitors indicates an important role for tyrosine phosphorylation events during EPEC subversion of host processes...

..These results demonstrate that although EPEC and EHEC recruit similar cytoskeletal proteins, there are also significant differences in pedestal composition...

..Cells with null alleles of both mammalian Nck genes are resistant to the effects of EPEC on the actin cytoskeleton. These results implicate Nck adaptors as host-cell determinants of EPEC virulence...

..Collectively, these results indicate that CesT is a Tir chaperone that may act as an anti-degradation factor by specifically binding to its amino-terminus, forming a multimeric stabilized complex...

..We highlight recent advances in the pathogenesis of enteropathogenic Escherichia coli, Salmonella Typhimurium, and Shigella flexneri. Each illustrates how bacterial pathogens can exert dramatic effects on the host cytoskeleton...

..In this review, we explore some of the host and pathogenic mechanisms mobilized in the two predominant clinical syndromes associated with infection with Salmonella enterica species: enterocolitis and typhoid...

..Our findings provide significant insights into bacterial virulence mechanisms and disease...

..Recent results suggest that Gram-positive pathogens may employ similar methods to deliver virulence factors into host cells...

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..Recent studies have shown that the fate of this vacuole is different in various cell types, and that the outcome of colonization is determined by both the infecting bacterium and defense mechanisms of the host cell...

..These results suggest that antibiotic perturbation of the microbiota can disrupt intestinal homeostasis and the integrity of intestinal defenses, which protect against invading pathogens and intestinal inflammation...

..The induction of in vivo disease correlates strongly with the degree of colonisation, suggesting that the colonisation advantage type III secretion genes afford the bacteria, contribute to, and are required for, full virulence...

..Here, we discuss how bacterial pathogens use an arsenal of secreted virulence proteins to modify the outcome of innate immune activation by altering how the immune system recognizes microbial invaders...

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..There is an exciting potential for the gene expression data generated in such studies to provide insights into host physiology, the pathophysiology of disease and novel therapeutics...

..Here we describe the manipulation of apoptosis by Salmonella and discuss the advantages that such actions may confer to the bacteria, and its implications in resistance to disease...

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..rodentium...

..coli and Citrobacter rodentium, and was absent from non-pathogenic strains of E. coli and non-LEE-containing pathogens. NleA was determined to play a key role in virulence of C. rodentium in a mouse infection model...

..These results suggest that the diarrhoea induced by A/E pathogens occurs as part of functional tight junction disruption...

..In addition, we will discuss areas where proteomics may help shape further investigation and discovery in this field...

..These data provide a framework for future biochemical analyses of host-pathogen interactions...

..Our data suggest that, unlike tight junctions, the desmosome protein levels and localization, as well as desmosome morphology, are unaltered during A/E pathogenesis...

..Such actions limit tissue damage and translocation of pathogenic and commensal bacteria across the epithelium...

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..Here, we present a novel murine model of severe and persistent intestinal fibrosis caused by chronic bacterial-induced colitis...

..rodentium infection. However, the selective expression of iNOS by uninfected but not infected cells suggests that this pathogen has developed mechanisms to locally limit its exposure to host-derived NO...

..This study demonstrates the presence of a previously undescribed direct influence of a mammalian innate host resistance locus on a pathogen at the genetic level...

..rodentium colonization of the mouse gut nor for inducing A/E lesions and colonic hyperplasia, thereby uncoupling colonization and disease from actin condensation for this A/E pathogen...

..From the use of bacterial toxins to investigate Rho family GTPases to in vitro studies of actin polymerization using Listeria and Shigella, the study of pathogenesis has provided important tools to probe cytoskeletal function...

..This review highlights recent advances in our understanding of the many interference strategies that are used by bacterial pathogens to undermine macrophage signalling...

..These data indicate that, contrary to previous indications, correct insertion and function of EscC secretin in the outer membrane depends not only on the sec-dependent secretion pathway but also on other type III apparatus components...

..Several lines of investigation indicate the feasibility of such strategies and justify further development of a vaccine targeting these significant intestinal pathogens...

..Recent studies have contributed to our understanding of bacterial adherence mechanisms and the consequences of receptor engagement; they have also highlighted alternative functions of cell adhesion molecules...

..Thus, this empirical MRSA-252 PIN provides a rich source for identifying critical proteins essential for network stability, many of which can be considered as prospective antimicrobial drug targets...

..These data suggest that massive uptake of extracellular fluid in S. typhimurium-infected epithelial cells is an event related to the invasion mechanisms used by this pathogen...

..Thus, we have characterized a region near the carboxyl-terminus of SigD which is important for phosphatase activity. We discuss how dephosphorylation of inositol phospholipids by SigD in vivo might contribute to the activation of Akt...

..Dysregulation of the homeostasis between mammals and their intestinal symbionts has been shown to predispose the host to enteric infection, and may lead to development of inflammatory bowel diseases...

..Collectively, these results suggest that sifA arose by horizontal gene transfer into Salmonella and its product is involved in a virulence-associated intracellular phenotype related to Salmonella-induced filament formation...

..Our findings demonstrate the requirement of the host cell endosomal system for maintenance of the SCV and that loss of this compartment allows increased replication of serovar Typhimurium in the cytosol of epithelial cells...

..Collectively, the results suggest a coordinated mechanism involving both Tir and CesT for type III effector injection into host cells...

..The enrichment of Salmonella effectors in DRMs on these intracellular membranes probably permits specific interactions with host cell molecules that are concentrated in these signalling platforms...

..These results directly demonstrate that virulence is selected via the fitness advantage it provides to the host-to-host cycle of pathogenic species...

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..To our knowledge, an innate defense regulator that counters infection by selective modulation of innate immunity without obvious toxicities has not been reported previously...

..Our findings demonstrate the essential role of microtubule dynamics in the formation of Sifs and the utility of this epitope tagging strategy for the study of bacterial type III secreted proteins...

..The following is a brief review of the way in which TTSSs and their effectors contribute to the pathogenic nature of the prototypic diarrheal pathogens Salmonella, Shigella, Yersinia and enteropathogenic Escherichia coli (EPEC)...

..In this Review, we focus on the recent advances in our understanding of the different pathogenic mechanisms that are used by various E. coli pathovars and how they cause disease in humans...

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..Thus, we demonstrate a functional and regulatory cross-talk between three chromosomal PAIs, SPI-1, SPI-2 and SPI-5, which has significant implications for the evolution and role of PAIs in bacterial pathogenesis...

..New evidence suggests that membrane insertion of the bacterial type III apparatus might turn on a calcium-dependent signaling pathway resulting in phagolysosomal fusion...

..We discuss some of the new strategies to combat bacterial virulence based on the inhibition of bacterial quorum sensing systems...

..This study further demonstrates that endocytic proteins are key components of EPEC pedestals and suggests a novel endocytosis subversion strategy employed by these extracellular bacteria...

..The altered localization of AQPs is partially dependent on the bacterial type III effector proteins EspF and EspG. We conclude that altered AQP localization may be a contributing factor to diarrhoea during bacterial infection...

..In summary, this work demonstrates that SseK1 and SseK2 are novel translocated proteins of serovar Typhimurium...

..These data indicate that destabilizing epithelial cell adherence is one of the factors increasing the risk of H. pylori-infected individuals developing gastric cancer...

..Finally, the sera of vaccinated mice contained antibodies to S, further suggesting a role for this protein in conferring protective immunity against SARS-CoV infection...

..This induction of expression precedes any documented SPI-2-dependent phases of typhoid and may be involved in preparing Salmonella to successfully resist the antimicrobial environment encountered within macrophages...

..These data suggest that overexpression of virulence-associated type III secretion genes can have an adverse effect on bacterial pathogenesis in vivo...

..Cumulatively, our data do not support the previous hypothesis that TlpA plays a role in the pathogenicity of Salmonella per se, but may suggest an alternative function for TlpA unrelated to host infection...

..These findings indicate that CesT is centrally involved in recruiting multiple type III effectors to the T3SS via EscN for efficient secretion, and functionally redefine the role of CesT in multiple type III effector interactions...

..Overall, we have identified a class of compounds that can be used as a tool to probe the mechanism(s) that regulates virulence gene expression in EPEC...

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..Microbes inhabiting the gut affect our health in profound and unexpected ways: new studies now show that these effects depend on synergistic and competitive interactions between the bacteria, which are influenced by diet...

..This system is well suited for screening clinical isolates and their mutants for specific genes conferring the invasiveness phenotype...

..This indicates possible similarities between the strategies used by pathogenic bacteria to elicit programmed cell death in both plant and animal hosts...

..While T and/or B lymphocytes are essential for host defense against C. rodentium, they also mediate much of the tissue pathology and disease symptoms that occur during infection...

..These data also suggest the existence of a previously unrecognized regulatory element within SPI-2 for the "effector operon" region downstream of sseD that might demarcate the expression of translocators and effectors...

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..Cumulatively, these results indicate that the ZirTS pathway plays a unique role as an antivirulence modulator during systemic disease and is involved in fine-tuning a host-pathogen balance during salmonellosis...

..Typhimurium. In this chapter, we analyze the different pathogen and host factors that play a role in the dynamic interaction between Salmonella and its host and their impact on disease...