The Experts below are selected from a list of 57630 Experts worldwide ranked by ideXlab platform
Pascale Serror - One of the best experts on this subject based on the ideXlab platform.
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Exploration of the role of the Virulence Factor ElrA during Enterococcus faecalis cell infection
Scientific Reports, 2018Co-Authors: Natalia Nunez, Aurélie Derré-bobillot, Stéphane Gaubert, Jean-marie Herry, Julien Deschamps, Yu Wei, Thomas Baranek, Mustapha Si-tahar, Romain Briandet, Pascale SerrorAbstract:Enterococcus faecalis, an organism generally not pathogenic for healthy humans, has the potential to cause disease in susceptible hosts. While it seems to be equipped to interact with and circumvent host immune defense, most of the molecular and cellular mechanisms underlying the enterococcal infectious process remain elusive. Here, we investigated the role of the Enterococcal Leucine Rich protein A (ElrA), an internalin-like protein of E. faecalis also known as a Virulence Factor. ElrA was previously shown to prevent adhesion to macrophages. We show that ElrA does not inhibit the basic phagocytic process, but is able to prevent sensing and migration of macrophages toward E. faecalis. Presence or absence of FHL2, a eukaryotic partner of ElrA, does not affect the ElrA-dependent mechanism preventing macrophage migration. However, we highlight a partial contribution of FHL2 in ElrA-mediated Virulence in vivo. Our results indicate that ElrA plays at least a dual role of which anti-phagocytic activity may contribute to dissemination of extracellular E. faecalis during infection.
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The Enterococcus faecalis Virulence Factor ElrA interacts with the human Four-and-a-Half LIM Domains Protein 2
Scientific Reports, 2017Co-Authors: Alexandre Jamet, Nicolas Lapaque, Rozenn Dervyn, Francesca Bugli, Naima Bermudez, Hervé M. Blottiere, Jean-claude Twizere, Maurizio Sanguinetti, Brunella Posteraro, Pascale SerrorAbstract:The commensal bacterium Enterococcus faecalis is a common cause of nosocomial infections worldwide. The increasing prevalence of multi-antibiotic resistant E. faecalis strains reinforces this public health concern. Despite numerous studies highlighting several pathology-related genetic traits, the molecular mechanisms of E. faecalis Virulence remain poorly understood. In this work, we studied 23 bacterial proteins that could be considered as Virulence Factors or involved in the Enterococcus interaction with the host. We systematically tested their interactions with human proteins using the Human ORFeome library, a set of 12,212 human ORFs, in yeast. Among the thousands of tested interactions, one involving the E. faecalis Virulence Factor ElrA and the human protein FHL2 was evidenced by yeast two-hybrid and biochemically confirmed. Further molecular characterizations allowed defining an FHL2-interacting domain (FID) of ElrA. Deletion of the FID led to an attenuated in vivo phenotype of the mutated strain clearly indicating that this interaction is likely to contribute to the multiFactorial Virulence of this opportunistic pathogen. Altogether, our results show that FHL2 is the first host cellular protein directly targeted by an E. faecalis Virulence Factor and that this interaction is involved in Enterococcus pathogenicity.
Bonnie L Bassler - One of the best experts on this subject based on the ideXlab platform.
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inhibitor mimetic mutations in the pseudomonas aeruginosa pqse enzyme reveal a protein protein interaction with the quorum sensing receptor rhlr that is vital for Virulence Factor production
ACS Chemical Biology, 2021Co-Authors: Isabelle R Taylor, Bonnie L Bassler, Jon E Paczkowski, Philip D Jeffrey, Brad R Henke, Chari D SmithAbstract:Pseudomonas aeruginosa is an opportunistic human pathogen that causes fatal infections. There exists an urgent need for new antimicrobial agents to combat P. aeruginosa. We conducted a screen for molecules that bind the Virulence-controlling protein PqsE and characterized hit compounds for inhibition of PqsE enzymatic activity. The binding conformations of two inhibitory molecules, BB391 and BB393, were identified by crystallography, and inhibitor binding was mimicked by the substitution of PqsE residues E182 and S285 with tryptophan. Comparison of the inhibitor-mimetic mutations to the catalytically inactive PqsE D73A protein demonstrated that catalysis is not responsible for the role PqsE plays in driving Virulence Factor production. Rather, the PqsE E182W protein fails to interact with the quorum-sensing receptor, RhlR, and our results suggest that it is this interaction that is responsible for promoting Virulence Factor production in P. aeruginosa. These findings provide a new route for drug discovery efforts targeting PqsE.
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the major vibrio cholerae autoinducer and its role in Virulence Factor production
Nature, 2007Co-Authors: Douglas A Higgins, Megan E Pomianek, Christina M Kraml, Ronald K Taylor, M F Semmelhack, Bonnie L BasslerAbstract:In a process called quorum sensing, certain bacteria can communicate with each other using chemical signalling molecules, allowing them to synchronize gene expression so that they act virtually as multicellular organisms. The cholera pathogen Vibrio cholerae uses quorum sensing to control Virulence and to organize the biofilms that contribute to the difficulties of treating the infection. Now the major V. cholerae quorum-sensing signalling molecule, an autoinducer called CAI-1, has been identified and characterized as (S)-3-hydroxytridecan-4-one, a molecule new to biology. Providing CAI-1 to the bacterium terminates the production of Factors required for pathogenicity, suggesting a possible new treatment for this major pathogen. Vibrio cholerae, the causative agent of cholera, employs quorum sensing to repress Virulence Factor expression at high cell density. The nature of one of the major signals is now revealed as (S)-3-hydroxytridecan-4-one constituting a new class of bacterial quorum sensing signalling molecules. Vibrio cholerae, the causative agent of the human disease cholera, uses cell-to-cell communication to control pathogenicity and biofilm formation1,2. This process, known as quorum sensing, relies on the secretion and detection of signalling molecules called autoinducers. At low cell density V. cholerae activates the expression of Virulence Factors and forms biofilms. At high cell density the accumulation of two quorum-sensing autoinducers represses these traits. These two autoinducers, cholerae autoinducer-1 (CAI-1) and autoinducer-2 (AI-2), function synergistically to control gene regulation, although CAI-1 is the stronger of the two signals. V. cholerae AI-2 is the furanosyl borate diester (2S,4S)-2-methyl-2,3,3,4-tetrahydroxytetrahydrofuran borate3. Here we describe the purification of CAI-1 and identify the molecule as (S)-3-hydroxytridecan-4-one, a new type of bacterial autoinducer. We provide a synthetic route to both the R and S isomers of CAI-1 as well as simple homologues, and we evaluate their relative activities. Synthetic (S)-3-hydroxytridecan-4-one functions as effectively as natural CAI-1 in repressing production of the canonical Virulence Factor TCP (toxin co-regulated pilus). These findings suggest that CAI-1 could be used as a therapy to prevent cholera infection and, furthermore, that strategies to manipulate bacterial quorum sensing hold promise in the clinical arena.
Alexandre Jamet - One of the best experts on this subject based on the ideXlab platform.
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The Enterococcus faecalis Virulence Factor ElrA interacts with the human Four-and-a-Half LIM Domains Protein 2
Scientific Reports, 2017Co-Authors: Alexandre Jamet, Nicolas Lapaque, Rozenn Dervyn, Francesca Bugli, Naima Bermudez, Hervé M. Blottiere, Jean-claude Twizere, Maurizio Sanguinetti, Brunella Posteraro, Pascale SerrorAbstract:The commensal bacterium Enterococcus faecalis is a common cause of nosocomial infections worldwide. The increasing prevalence of multi-antibiotic resistant E. faecalis strains reinforces this public health concern. Despite numerous studies highlighting several pathology-related genetic traits, the molecular mechanisms of E. faecalis Virulence remain poorly understood. In this work, we studied 23 bacterial proteins that could be considered as Virulence Factors or involved in the Enterococcus interaction with the host. We systematically tested their interactions with human proteins using the Human ORFeome library, a set of 12,212 human ORFs, in yeast. Among the thousands of tested interactions, one involving the E. faecalis Virulence Factor ElrA and the human protein FHL2 was evidenced by yeast two-hybrid and biochemically confirmed. Further molecular characterizations allowed defining an FHL2-interacting domain (FID) of ElrA. Deletion of the FID led to an attenuated in vivo phenotype of the mutated strain clearly indicating that this interaction is likely to contribute to the multiFactorial Virulence of this opportunistic pathogen. Altogether, our results show that FHL2 is the first host cellular protein directly targeted by an E. faecalis Virulence Factor and that this interaction is involved in Enterococcus pathogenicity.
Nicolas Lapaque - One of the best experts on this subject based on the ideXlab platform.
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The Enterococcus faecalis Virulence Factor ElrA interacts with the human Four-and-a-Half LIM Domains Protein 2
Scientific Reports, 2017Co-Authors: Alexandre Jamet, Nicolas Lapaque, Rozenn Dervyn, Francesca Bugli, Naima Bermudez, Hervé M. Blottiere, Jean-claude Twizere, Maurizio Sanguinetti, Brunella Posteraro, Pascale SerrorAbstract:The commensal bacterium Enterococcus faecalis is a common cause of nosocomial infections worldwide. The increasing prevalence of multi-antibiotic resistant E. faecalis strains reinforces this public health concern. Despite numerous studies highlighting several pathology-related genetic traits, the molecular mechanisms of E. faecalis Virulence remain poorly understood. In this work, we studied 23 bacterial proteins that could be considered as Virulence Factors or involved in the Enterococcus interaction with the host. We systematically tested their interactions with human proteins using the Human ORFeome library, a set of 12,212 human ORFs, in yeast. Among the thousands of tested interactions, one involving the E. faecalis Virulence Factor ElrA and the human protein FHL2 was evidenced by yeast two-hybrid and biochemically confirmed. Further molecular characterizations allowed defining an FHL2-interacting domain (FID) of ElrA. Deletion of the FID led to an attenuated in vivo phenotype of the mutated strain clearly indicating that this interaction is likely to contribute to the multiFactorial Virulence of this opportunistic pathogen. Altogether, our results show that FHL2 is the first host cellular protein directly targeted by an E. faecalis Virulence Factor and that this interaction is involved in Enterococcus pathogenicity.
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cyclic beta 1 2 glucan is a brucella Virulence Factor required for intracellular survival
Nature Immunology, 2005Co-Authors: Beatriz Arellanoreynoso, Nicolas Lapaque, Susana Salcedo, Gabriel Briones, Andres Eduardo Ciocchini, Rodolfo A Ugalde, Edgardo Moreno, Ignacio Moriyón, Jean-pierre GorvelAbstract:Pathogenic brucella bacteria have developed strategies to persist for prolonged periods of time in host cells, avoiding innate immune responses. Here we show that the cyclic beta-1,2-glucans (CbetaG) synthesized by brucella is important for circumventing host cell defenses. CbetaG acted in lipid rafts found on host cell membranes. CbetaG-deficient mutants failed to prevent phagosome-lysosome fusion and could not replicate. However, when treated with purified CbetaG or synthetic methyl-beta-cyclodextrin, the mutants were able to control vacuole maturation by avoiding lysosome fusion, and this allowed intracellular brucella to survive and reach the endoplasmic reticulum. Fusion between the endoplasmic reticulum and the brucella-containing vacuole depended on the brucella Virulence type IV secretion system but not on CbetaG. Brucella CbetaG is thus a Virulence Factor that interacts with lipid rafts and contributes to pathogen survival.
Lianhui Zhang - One of the best experts on this subject based on the ideXlab platform.
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rice bacterial blight pathogen xanthomonas oryzae pv oryzae produces multiple dsf family signals in regulation of Virulence Factor production
BMC Microbiology, 2010Co-Authors: Yawen He, Jien Wu, Lianhui ZhangAbstract:Background Xanthomonas oryzae pv. oryzae (Xoo) is the causal agent of rice bacterial blight disease. Xoo produces a range of Virulence Factors, including EPS, extracellular enzyme, iron-chelating siderophores, and type III-secretion dependent effectors, which are collectively essential for Virulence. Genetic and genomics evidence suggest that Xoo might use the diffusible signal Factor (DSF) type quorum sensing (QS) system to regulate the Virulence Factor production. However, little is known about the chemical structure of the DSF-like signal(s) produced by Xoo and the Factors influencing the signal production.
