The Experts below are selected from a list of 276 Experts worldwide ranked by ideXlab platform
Francois Vandenesch - One of the best experts on this subject based on the ideXlab platform.
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staphylococcus aureus hemolysins bi component Leukocidins and cytolytic peptides a redundant arsenal of membrane damaging virulence factors
Frontiers in Cellular and Infection Microbiology, 2012Co-Authors: Gerard Lina, Francois Vandenesch, Thomas HenryAbstract:One key aspect of S. aureus virulence lies in its ability to target the host cell membrane with a large number of membrane-damaging toxins and peptides. In this review, we describe the hemolysins, the bi-component Leukocidins, which include the Panton Valentine Leukocidin, LukAB/GH, LukED and the cytolytic peptides (Phenol Soluble Modulins). While at first glance, all these factors might appear redundant, it is now clear that some of these factors play specific roles in certain S. aureus life stages and diseases or target specific cell types or species. Here, we present an update of the literature on toxins receptors and their cell type and species specificities. Furthermore, we review epidemiological studies and animal models illustrating a role of these membrane-damaging factors in various diseases. Finally, we emphasize the interplay of these factors with the host immune system and highlight all their non-lytic functions.
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Staphylococcus aureus hemolysins, bi-component Leukocidins, and cytolytic peptides: a redundant arsenal of membrane-damaging virulence factors?
Frontiers in Cellular and Infection Microbiology, 2012Co-Authors: Francois Vandenesch, G. Lina, Thomas HenryAbstract:One key aspect of the virulence of Staphylococcus aureus lies in its ability to target the host cell membrane with a large number of membrane-damaging toxins and peptides. In this review, we describe the hemolysins, the bi-component Leukocidins (which include the Panton Valentine Leukocidin, LukAB/GH, and LukED), and the cytolytic peptides (phenol soluble modulins). While at first glance, all of these factors might appear redundant, it is now clear that some of these factors play specific roles in certain S. aureus life stages and diseases or target specific cell types or species. In this review, we present an update of the literature on toxin receptors and their cell type and species specificities. Furthermore, we review epidemiological studies and animal models illustrating the role of these membrane-damaging factors in various diseases. Finally, we emphasize the interplay of these factors with the host immune system and highlight all their non-lytic functions.
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Panton-Valentine Leukocidin-positive Staphylococcus aureus strains are associated with follicular skin infections.
Dermatology (Basel Switzerland), 2011Co-Authors: Pascal Del Giudice, Gerard Lina, Michele Bes, Francois Vandenesch, Thomas Hubiche, Véronique Blanc, Laurent Roudière, Jerome EtienneAbstract:Background/Aims: Panton-Valentine Leukocidin (PVL)-positive Staphylococcus aureus have been associated with suppurative infections; however, their precise role in
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Panton-valentine Leukocidin and staphyloccoccal skin infections in schoolchildren.
Emerging infectious diseases, 2004Co-Authors: Karim Boubaker, Francois Vandenesch, Patrick Diebold, Dominique S. Blanc, Gérard Praz, Georges Dupuis, N. TroilletAbstract:The Panton-Valentine Leukocidin is associated with staphylococcal skin and pulmonary infections. We describe a school outbreak of skin infections and the public health response to it. Nasal carriage of a Panton-Valentine Leukocidin-positive Staphylococcus aureus clone was detected only in previously ill classmates and their family members.
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community acquired methicillin resistant staphylococcus aureus infections in france emergence of a single clone that produces panton valentine Leukocidin
Clinical Infectious Diseases, 2002Co-Authors: Philippe Dufour, Jerome Etienne, Gerard Lina, Michele Bes, Francois Vandenesch, Y. Gillet, D. Floret, Herve RichetAbstract:To characterize the clinical and bacteriologic characteristics ofcommunity-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) infections, we reviewed 14 cases that were diagnosed in previously healthy patients during an 18-month period in France. Eleven patients had skin or soft-tissue infections. Two patients died of CA-MRSA necrotizing pneumonia. A case of pleurisy occurred in a child who acquired CA-MRSA from his mother, who had a breast abscess. The Panton-Valentine Leukocidin genes and the lukE-lukD Leukocidin genes were detected in all 14 isolates. The clonal origin of all of the isolates was demonstrated on the basis of their pulsotypes and antibiotic resistance profiles. All isolates had an agr3 allele. The combination of the Panton-Valentine Leukocidin determinant (which encodes a virulence factor for primary skin infection and pneumonia) with the mecA gene (which confers antibiotic resistance and epidemicity) appears to have created a superadapted S. aureus strain that is spreading in the community.
Gerard Lina - One of the best experts on this subject based on the ideXlab platform.
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Outbreak of Panton-Valentine Leukocidin-Associated Methicillin-Susceptible Staphylococcus Aureus Infection in a Rugby Team, France, 2010-2011
Emerging infectious diseases, 2016Co-Authors: Elodie Couvé-deacon, Gerard Lina, Anne Tristan, N. Pestourie, Christian Faure, Valérie Doffoel-hantz, Fabien Garnier, Frédéric Laurent, Marie-cécile PloyAbstract:Staphylococcus aureus strains that produce Panton-Valentine Leukocidin are known to cause community infections. We describe an outbreak of skin abscesses caused by Panton-Valentine Leukocidin-producing methicillin-susceptible S. aureus (clonal complex 121) in a professional rugby team in France during July 2010-February 2011. Eight team members were carriers; 7 had skin abscesses.
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staphylococcus aureus hemolysins bi component Leukocidins and cytolytic peptides a redundant arsenal of membrane damaging virulence factors
Frontiers in Cellular and Infection Microbiology, 2012Co-Authors: Gerard Lina, Francois Vandenesch, Thomas HenryAbstract:One key aspect of S. aureus virulence lies in its ability to target the host cell membrane with a large number of membrane-damaging toxins and peptides. In this review, we describe the hemolysins, the bi-component Leukocidins, which include the Panton Valentine Leukocidin, LukAB/GH, LukED and the cytolytic peptides (Phenol Soluble Modulins). While at first glance, all these factors might appear redundant, it is now clear that some of these factors play specific roles in certain S. aureus life stages and diseases or target specific cell types or species. Here, we present an update of the literature on toxins receptors and their cell type and species specificities. Furthermore, we review epidemiological studies and animal models illustrating a role of these membrane-damaging factors in various diseases. Finally, we emphasize the interplay of these factors with the host immune system and highlight all their non-lytic functions.
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Panton-Valentine Leukocidin-positive Staphylococcus aureus strains are associated with follicular skin infections.
Dermatology (Basel Switzerland), 2011Co-Authors: Pascal Del Giudice, Gerard Lina, Michele Bes, Francois Vandenesch, Thomas Hubiche, Véronique Blanc, Laurent Roudière, Jerome EtienneAbstract:Background/Aims: Panton-Valentine Leukocidin (PVL)-positive Staphylococcus aureus have been associated with suppurative infections; however, their precise role in
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community acquired methicillin resistant staphylococcus aureus infections in france emergence of a single clone that produces panton valentine Leukocidin
Clinical Infectious Diseases, 2002Co-Authors: Philippe Dufour, Jerome Etienne, Gerard Lina, Michele Bes, Francois Vandenesch, Y. Gillet, D. Floret, Herve RichetAbstract:To characterize the clinical and bacteriologic characteristics ofcommunity-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) infections, we reviewed 14 cases that were diagnosed in previously healthy patients during an 18-month period in France. Eleven patients had skin or soft-tissue infections. Two patients died of CA-MRSA necrotizing pneumonia. A case of pleurisy occurred in a child who acquired CA-MRSA from his mother, who had a breast abscess. The Panton-Valentine Leukocidin genes and the lukE-lukD Leukocidin genes were detected in all 14 isolates. The clonal origin of all of the isolates was demonstrated on the basis of their pulsotypes and antibiotic resistance profiles. All isolates had an agr3 allele. The combination of the Panton-Valentine Leukocidin determinant (which encodes a virulence factor for primary skin infection and pneumonia) with the mecA gene (which confers antibiotic resistance and epidemicity) appears to have created a superadapted S. aureus strain that is spreading in the community.
Guang Yang - One of the best experts on this subject based on the ideXlab platform.
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Novel human monoclonal antibodies targeting the F subunit of Leukocidins reduce disease progression and mortality caused by Staphylococcus aureus
BMC Microbiology, 2018Co-Authors: Chendi Jing, Chenghua Liu, Yaping Gao, Zhangchun Guan, Fangjie Liu, Bo Xuan, Yanyan Yu, Yu Liu, Guang YangAbstract:BackgroundStaphylococcus aureus is a leading cause of Gram-positive bacterial infections worldwide; however, the treatment of S. aureus infection has become increasingly difficult due to the prevalence of methicillin-resistant S. aureus strains, highlighting the urgent need for the development of novel strategies. The complexity of S. aureus pathogenesis relies on virulence factors. Recent studies have demonstrated that Leukocidins expressed by the majority of clinical isolates play important roles in the pathogenesis of S. aureus.ResultsIn this study, we developed three human monoclonal antibodies against all F-components of Leukocidins HlgABC, LukSF, and LukED with high affinity. These antibodies were found to be capable of blocking Leukocidin-mediated cell lysis in vitro. Furthermore, the antibodies dramatically reduced disease progression and mortality after S. aureus infection in vivo.ConclusionsOur findings revealed that neutralizing bicomponent Leukocidins may be a promising strategy to combat infections caused by S. aureus.
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Novel human monoclonal antibodies targeting the F subunit of Leukocidins reduce disease progression and mortality caused by Staphylococcus aureus.
BMC microbiology, 2018Co-Authors: Chendi Jing, Yaping Gao, Zhangchun Guan, Bo Xuan, Yu Liu, Liu Chenghua, Liu Fangjie, Guang YangAbstract:Staphylococcus aureus is a leading cause of Gram-positive bacterial infections worldwide; however, the treatment of S. aureus infection has become increasingly difficult due to the prevalence of methicillin-resistant S. aureus strains, highlighting the urgent need for the development of novel strategies. The complexity of S. aureus pathogenesis relies on virulence factors. Recent studies have demonstrated that Leukocidins expressed by the majority of clinical isolates play important roles in the pathogenesis of S. aureus. In this study, we developed three human monoclonal antibodies against all F-components of Leukocidins HlgABC, LukSF, and LukED with high affinity. These antibodies were found to be capable of blocking Leukocidin-mediated cell lysis in vitro. Furthermore, the antibodies dramatically reduced disease progression and mortality after S. aureus infection in vivo. Our findings revealed that neutralizing bicomponent Leukocidins may be a promising strategy to combat infections caused by S. aureus.
Angelino T. Tromp - One of the best experts on this subject based on the ideXlab platform.
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Studying Staphylococcal Leukocidins: A Challenging Endeavor.
Frontiers in microbiology, 2020Co-Authors: Angelino T. Tromp, Jos A. G. Van StrijpAbstract:Staphylococcus aureus is a well-known colonizer of the human skin and nose, but also a human pathogen that causes a wide spectrum of diseases. It is well established that S. aureus secretes an arsenal of virulence factors that have evolved to circumvent the human immune system. A major group of S. aureus virulence factors is the bi-component β-barrel pore-forming toxins, also known as Leukocidins. These pore-forming toxins target specific cells of the innate and adaptive immune system by interacting with specific receptors expressed on the cell membrane. Even though still heavily debated, clinical and epidemiological studies suggest the involvement of one of the bi-component toxin, Panton-Valentine Leukocidin (PVL), as an important factor contributing to the epidemic spread and increased virulence of CA-MRSA strains. However, the host- and cell-specificity of PVL and other Leukocidins, and the lack of adequate in vivo models, fuels the controversy and impairs the appropriate assessment of their role in S. aureus pathophysiology. Currently, the mechanisms of pore-formation and the contribution of PVL and other Leukocidins to S. aureus pathophysiology are incompletely understood. This review summarizes our current understanding of Leukocidin pore-formation, knowledge gaps, and highlights recent findings identifying novel host-factors involved in the toxin-host interface. As a result, this review furthers emphasizes the complexity behind S. aureus Leukocidin cytotoxicity and the challenges associated in the quest to study and understand these major virulence factors.
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Host-Receptor Post-Translational Modifications Refine Staphylococcal Leukocidin Cytotoxicity.
Toxins, 2020Co-Authors: Angelino T. Tromp, Carla J. C. De Haas, Kok P. M. Van Kessel, Michiel Van Gent, Joris P. Jansen, Bart W. Bardoel, Lisette M Scheepmaker, Anneroos Velthuizen, Michael Boettcher, Michael T. McmanusAbstract:Staphylococcal bi-component pore-forming toxins, also known as Leukocidins, target and lyse human phagocytes in a receptor-dependent manner. S-components of the Leukocidins Panton-Valentine Leukocidin (PVL), γ-haemolysin AB (HlgAB) and CB (HlgCB), and Leukocidin ED (LukED) specifically employ receptors that belong to the class of G-protein coupled receptors (GPCRs). Although these receptors share a common structural architecture, little is known about the conserved characteristics of the interaction between Leukocidins and GPCRs. In this study, we investigated host cellular pathways contributing to susceptibility towards S. aureus Leukocidin cytotoxicity. We performed a genome-wide CRISPR/Cas9 library screen for toxin-resistance in U937 cells sensitized to Leukocidins by ectopic expression of different GPCRs. Our screen identifies post-translational modification (PTM) pathways involved in the sulfation and sialylation of the Leukocidin-receptors. Subsequent validation experiments show differences in the impact of PTM moieties on Leukocidin toxicity, highlighting an additional layer of refinement and divergence in the staphylococcal host-pathogen interface. Leukocidin receptors may serve as targets for anti-staphylococcal interventions and understanding toxin-receptor interactions will facilitate the development of innovative therapeutics. Variations in the genes encoding PTM pathways could provide insight into observed differences in susceptibility of humans to infections with S. aureus.
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Human CD45 is an F-component-specific receptor for the staphylococcal toxin Panton-Valentine Leukocidin
Nature Microbiology, 2018Co-Authors: Angelino T. Tromp, Carla J. C. De Haas, Kok P. M. Van Kessel, Michiel Van Gent, Pauline Abrial, Amandine Martin, Joris P. Jansen, Bart W. Bardoel, Elisabeth Kruse, Emilie BourdonnayAbstract:The staphylococcal bi-component Leukocidins Panton-Valentine Leukocidin (PVL) and γ-haemolysin CB (HlgCB) target human phagocytes. Binding of the toxins' S-components to human complement C5a receptor 1 (C5aR1) contributes to cellular tropism and human specificity of PVL and HlgCB. To investigate the role of both Leukocidins during infection, we developed a human C5aR1 knock-in (hC5aR1KI) mouse model. HlgCB, but unexpectedly not PVL, contributed to increased bacterial loads in tissues of hC5aR1KI mice. Compared to humans, murine hC5aR1KI neutrophils showed a reduced sensitivity to PVL, which was mediated by the toxin's F-component LukF-PV. By performing a genome-wide CRISPR-Cas9 screen, we identified CD45 as a receptor for LukF-PV. The human-specific interaction between LukF-PV and CD45 provides a molecular explanation for resistance of hC5aR1KI mouse neutrophils to PVL and probably contributes to the lack of a PVL-mediated phenotype during infection in these mice. This study demonstrates an unsuspected role of the F-component in driving the sensitivity of human phagocytes to PVL.
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Human CD45 is an F-component-specific receptor for the staphylococcal toxin Panton–Valentine Leukocidin
Nature microbiology, 2018Co-Authors: Angelino T. Tromp, Carla J. C. De Haas, Kok P. M. Van Kessel, Michiel Van Gent, Pauline Abrial, Amandine Martin, Joris P. Jansen, Bart W. Bardoel, Elisabeth Kruse, Emilie BourdonnayAbstract:The staphylococcal bi-component Leukocidins Panton–Valentine Leukocidin (PVL) and γ-haemolysin CB (HlgCB) target human phagocytes. Binding of the toxins’ S-components to human complement C5a receptor 1 (C5aR1) contributes to cellular tropism and human specificity of PVL and HlgCB. To investigate the role of both Leukocidins during infection, we developed a human C5aR1 knock-in (hC5aR1KI) mouse model. HlgCB, but unexpectedly not PVL, contributed to increased bacterial loads in tissues of hC5aR1KI mice. Compared to humans, murine hC5aR1KI neutrophils showed a reduced sensitivity to PVL, which was mediated by the toxin’s F-component LukF-PV. By performing a genome-wide CRISPR–Cas9 screen, we identified CD45 as a receptor for LukF-PV. The human-specific interaction between LukF-PV and CD45 provides a molecular explanation for resistance of hC5aR1KI mouse neutrophils to PVL and probably contributes to the lack of a PVL-mediated phenotype during infection in these mice. This study demonstrates an unsuspected role of the F-component in driving the sensitivity of human phagocytes to PVL. Human CD45 serves as a receptor for the Staphylococcus aureus Panton–Valentine Leukocidin (PVL) F-component LukF-PV and contributes to the species specificity behind PVL intoxication of human immune cells.
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human cd45 is an f component specific receptor for the staphylococcal toxin panton valentine Leukocidin
Nature microbiology, 2018Co-Authors: Angelino T. Tromp, Carla J. C. De Haas, Kok P. M. Van Kessel, Michiel Van Gent, Pauline Abrial, Amandine Martin, Joris P. Jansen, Bart W. Bardoel, Elisabeth KruseAbstract:The staphylococcal bi-component Leukocidins Panton–Valentine Leukocidin (PVL) and γ-haemolysin CB (HlgCB) target human phagocytes. Binding of the toxins’ S-components to human complement C5a receptor 1 (C5aR1) contributes to cellular tropism and human specificity of PVL and HlgCB. To investigate the role of both Leukocidins during infection, we developed a human C5aR1 knock-in (hC5aR1KI) mouse model. HlgCB, but unexpectedly not PVL, contributed to increased bacterial loads in tissues of hC5aR1KI mice. Compared to humans, murine hC5aR1KI neutrophils showed a reduced sensitivity to PVL, which was mediated by the toxin’s F-component LukF-PV. By performing a genome-wide CRISPR–Cas9 screen, we identified CD45 as a receptor for LukF-PV. The human-specific interaction between LukF-PV and CD45 provides a molecular explanation for resistance of hC5aR1KI mouse neutrophils to PVL and probably contributes to the lack of a PVL-mediated phenotype during infection in these mice. This study demonstrates an unsuspected role of the F-component in driving the sensitivity of human phagocytes to PVL. Human CD45 serves as a receptor for the Staphylococcus aureus Panton–Valentine Leukocidin (PVL) F-component LukF-PV and contributes to the species specificity behind PVL intoxication of human immune cells.
Binh An Diep - One of the best experts on this subject based on the ideXlab platform.
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protective efficacy of monoclonal antibodies neutralizing alpha hemolysin and bicomponent Leukocidins in a rabbit model of staphylococcus aureus necrotizing pneumonia
Antimicrobial Agents and Chemotherapy, 2019Co-Authors: Nhu T Q Nguyen, Vuvi G Tran, Emmanuelle Gras, Yanjie Mao, David H Jung, Christine Tkaczyk, Bret R Sellman, Binh An DiepAbstract:Staphylococcus aureus is a major human pathogen that causes a wide range of infections by producing an arsenal of cytotoxins. We found that passive immunization with either a monoclonal antibody (MAb) neutralizing alpha-hemolysin or a broadly cross-reactive MAb neutralizing Panton-Valentine Leukocidin, Leukocidin ED, and gamma-hemolysins HlgAB and HlgCB conferred only partial protection, whereas the combination of those two MAbs conferred significant protection in a rabbit model of necrotizing pneumonia caused by the USA300 methicillin-resistant S. aureus epidemic clone.
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improved protection in a rabbit model of community associated methicillin resistant staphylococcus aureus necrotizing pneumonia upon neutralization of Leukocidins in addition to alpha hemolysin
Antimicrobial Agents and Chemotherapy, 2016Co-Authors: Binh An Diep, Zehra Visram, Harald Rouha, Lukas Stulik, Etyene Castro Dip, Gabor Nagy, Eszter NagyAbstract:Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA), especially the USA300 pulsotype, is a frequent cause of skin and soft tissue infections and severe pneumonia. Despite appropriate antibiotic treatment, complications are common and pneumonia is associated with high mortality. S. aureus strains express multiple cytotoxins, including alpha-hemolysin (Hla) and up to five bicomponent Leukocidins that specifically target phagocytic cells for lysis. CA-MRSA USA300 strains carry the genes for all six cytotoxins. Species specificity of the Leukocidins greatly contributes to the ambiguity regarding their role in S. aureus pathogenesis. We performed a comparative analysis of the Leukocidin susceptibility of human, rabbit, and mouse polymorphonuclear leukocytes (PMNs) to assess the translational value of mouse and rabbit S. aureus models. We found that mouse PMNs were largely resistant to LukSF-PV, HlgAB, and HlgCB and susceptible only to LukED, whereas rabbit and human PMNs were highly sensitive to all these cytotoxins. In the rabbit pneumonia model with a USA300 CA-MRSA strain, passive immunization with a previously identified human monoclonal antibody (MAb), Hla-F#5, which cross-neutralizes Hla, LukSF-PV, HlgAB, HlgCB, and LukED, provided full protection, whereas an Hla-specific MAb was only partially protective. In the mouse USA300 CA-MRSA pneumonia model, both types of antibodies demonstrated full protection, suggesting that Hla, but not Leukocidin(s), is the principal virulence determinant in mice. As the rabbit recapitulates the high susceptibility to Leukocidins characteristic of humans, this species represents a valuable model for assessing novel, cytotoxin-targeting anti-S. aureus therapeutic approaches.