FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2040284417> ?p ?o ?g. }

• W2040284417 endingPage "424" @default.
• W2040284417 startingPage "423" @default.
• W2040284417 abstract "Epidemics of community-acquired Staphylococcus aureus are caused by strains producing high concentrations of phenol-soluble modulins (PSMs). How neutrophils sense PSMs is revealed in this issue of Cell Host & Microbe. Such interactions are key to infection outcome and may be the basis for development of new treatment strategies. Epidemics of community-acquired Staphylococcus aureus are caused by strains producing high concentrations of phenol-soluble modulins (PSMs). How neutrophils sense PSMs is revealed in this issue of Cell Host & Microbe. Such interactions are key to infection outcome and may be the basis for development of new treatment strategies. Upon colonizing a new host, an infectious agent must be able to resist, subvert, or escape the action of the immune system in order for the agent to remain within the host. Many microorganisms are able to do this without causing disease, but some are pathogenic by virtue of their successful evasion of innate defenses, such as antimicrobial peptides and killing by phagocytic leukocytes. It is the balance struck between host response and pathogen countermeasures that determines the severity of disease. A ubiquitous member of the normal human microflora, the Gram-positive bacterium Staphylococcus aureus is a significant cause of human morbidity and mortality. Colonization can occur in community or healthcare settings, and infections are often difficult to treat because of widespread antibiotic resistance; methicillin-resistant S. aureus (MRSA) strains are common. Individuals who succumb to healthcare-associated strains (HA-MRSA) usually have predisposing risk factors, but community-associated infections (CA-MRSA) can occur in otherwise healthy individuals who are neither predisposed to infection nor exposed to any healthcare setting, suggesting that these strains are more virulent than HA-MRSA. Indeed, interest in CA-MRSA infections has grown over the past decade because of its epidemic spread throughout much of the developed world, which has further increased the total global burden of S. aureus disease (Graves et al., 2010Graves S.F. Kobayashi S.D. DeLeo F.R. J. Mol. Med. 2010; 88: 109-114Crossref PubMed Scopus (58) Google Scholar). Most CA-MRSA diseases are of skin and soft tissue and are similar to those caused by methicillin-sensitive S. aureus; however, these strains also have the ability to cause severe invasive diseases such as pneumonia, myositis, and necrotising fasciitis. Regardless of severity, disease is due, in large part, to the ability of the pathogen to evade host innate immunity. CA-MRSA pathologies are often characterized by influx of neutrophils at the site of infection, their subsequent lysis, and concomitant tissue damage (Graves et al., 2010Graves S.F. Kobayashi S.D. DeLeo F.R. J. Mol. Med. 2010; 88: 109-114Crossref PubMed Scopus (58) Google Scholar). S. aureus can produce a range of toxins, one of which, Panton-Valentine leukocidin (PVL), has been linked with CA-MRSA and is the subject of intensive study. In experiments to determine its role as a virulence factor in animal models of S. aureus disease, mixed results have been obtained (Graves et al., 2010Graves S.F. Kobayashi S.D. DeLeo F.R. J. Mol. Med. 2010; 88: 109-114Crossref PubMed Scopus (58) Google Scholar). Furthermore, there are reports of CA-MRSA strains that lack PVL (Zhang et al., 2008Zhang K. McClure J.A. Elsayed S. Tan J. Conly J.M. J. Infect. Dis. 2008; 197: 195-204Crossref PubMed Scopus (62) Google Scholar), suggesting that the molecular basis for the enhanced virulence in these strains cannot be explained solely by the presence of this toxin. S. aureus also produces several small (c. 20 amino acid) phenol-soluble modulin (PSM) peptides that efficiently destroy host neutrophils at micromolar concentrations in vitro, most probably by disruption of cell membranes. Seven of these PSMs are encoded by the core genome of S. aureus, with one more sometimes being found on a mobile genetic element found in HA-MRSA strains (Wang et al., 2007Wang R. Braughton K.R. Kretschmer D. Bach T.H. Queck S.Y. Li M. Kennedy A.D. Dorward D.W. Klebanoff S.J. Peschel A. et al.Nat. Med. 2007; 13: 1510-1514Crossref PubMed Scopus (734) Google Scholar, Queck et al., 2009Queck S.Y. Khan B.A. Wang R. Bach T.H. Kretschmer D. Chen L. Kreiswirth B.N. Peschel A. Deleo F.R. Otto M. PLoS Pathog. 2009; 5: e1000533Crossref PubMed Scopus (152) Google Scholar). Relative to other S. aureus strains, CA-MRSA produce much higher concentrations of PSMs, and it is this difference that accounts, at least in part, for their potent virulence (Wang et al., 2007Wang R. Braughton K.R. Kretschmer D. Bach T.H. Queck S.Y. Li M. Kennedy A.D. Dorward D.W. Klebanoff S.J. Peschel A. et al.Nat. Med. 2007; 13: 1510-1514Crossref PubMed Scopus (734) Google Scholar). These small α-helical amphipathic peptides carry an N-terminal N-formyl methionine, which is detected by the host immune system as a signal for bacterial infection, as only prokaryotes commence protein biosynthesis with a formyl methionine (Fu et al., 2006Fu H. Karlsson J. Bylund J. Movitz C. Karlsson A. Dahlgren C. J. Leukoc. Biol. 2006; 79: 247-256Crossref PubMed Scopus (132) Google Scholar). In addition to their cytolytic activity, PSMs have powerful chemoattractant properties, which accounts for the leukocyte influx observed in CA-MRSA disease. Formyl peptide receptors found on neutrophils are part of the G protein-coupled receptor superfamily and are responsible for sensing PSMs and eliciting cell migration. It is the molecular basis of this recognition that is addressed by Kretschmer et al., 2010Kretschmer D. Gleske A. Rautenberg M. Wang R. Köberle M. Bohn E. Schönenberg T. Rabiet M. Boulay F. Klebanoff S.J. et al.Cell Host Microbe. 2010; 7 (this issue): 463-473Abstract Full Text Full Text PDF PubMed Scopus (188) Google Scholar in this issue of Cell Host & Microbe. Dorothee Kretschmer and Anne-Katherine Gleske from Andreas Peschel's laboratory have, along with colleagues, discovered that the human formyl peptide receptor 2 (FPR2/ALX) present on neutrophils is able to sense PSMs at nanomolar concentrations and initiate the proinflammatory response characteristic of much CA-MRSA disease. Of interest, S. aureus subverts signaling via formyl peptide receptors in more than one way. The anti-inflammatory chemotaxis inhibitory protein of S. aureus (CHIPS) blocks peptide recognition by formyl peptide receptor 1 (FPR1) (de Haas et al., 2004de Haas C.J.C. Veldkamp K.E. Peschel A. Weerkamp F. Van Wamel W.J.B. Heezius E.C. Poppelier M.J.J.G. Van Kessel K.P.M. van Strijp J.A.G. J. Exp. Med. 2004; 199: 687-695Crossref PubMed Scopus (317) Google Scholar). The pathogen also produces an anti-inflammatory antagonist of FPR2/ALX, known as FPR2/ALX inhibitory protein (FLIPr), which impairs neutrophil responses to FPR2/ALX agonists and FPR1 agonists at high concentrations (Prat et al., 2006Prat C. Bestebroer J. de Haas C.J.C. van Strijp J.A.G. van Kessel K.P.M. J. Immunol. 2006; 177: 8017-8026PubMed Google Scholar). Furthermore, a peptide called FLIPr-like has recently been identified, which is a potent inhibitor of both FPR1- and FPR2/ALX-mediated neutrophil activation (Prat et al., 2009Prat C. Haas P.J. Bestebroer J. de Haas C.J.C. van Strijp J.A.G. van Kessel K.P.M. J. Immunol. 2009; 183: 6569-6578Crossref PubMed Scopus (54) Google Scholar). Given the lengths that S. aureus appears to go to in order to suppress signaling through formyl peptide receptors, we could be forgiven for imagining that inhibition of these signaling events would increase the pathogenic potential of S. aureus, and, in many strains, that is indeed what happens. But Kretschmer et al., 2010Kretschmer D. Gleske A. Rautenberg M. Wang R. Köberle M. Bohn E. Schönenberg T. Rabiet M. Boulay F. Klebanoff S.J. et al.Cell Host Microbe. 2010; 7 (this issue): 463-473Abstract Full Text Full Text PDF PubMed Scopus (188) Google Scholar have demonstrated that PSMs activate cells by signaling specifically through FPR2/ALX, causing influx of neutrophils at the site of infection, where they are then lysed, presumably by higher local concentrations of PSMs. How S. aureus ensures appropriate expression of these antagonists relative to PSMs remains to be elucidated. It is noteworthy that FPR2/ALX appears to play no part in PSM cytotoxicity (Kretschmer et al., 2010Kretschmer D. Gleske A. Rautenberg M. Wang R. Köberle M. Bohn E. Schönenberg T. Rabiet M. Boulay F. Klebanoff S.J. et al.Cell Host Microbe. 2010; 7 (this issue): 463-473Abstract Full Text Full Text PDF PubMed Scopus (188) Google Scholar). Clearly, the success of CA-MRSA strains is linked to their ability to produce relatively large concentrations of PSMs, which, in turn, have the ability to attract phagocytic neutrophils (Wang et al., 2007Wang R. Braughton K.R. Kretschmer D. Bach T.H. Queck S.Y. Li M. Kennedy A.D. Dorward D.W. Klebanoff S.J. Peschel A. et al.Nat. Med. 2007; 13: 1510-1514Crossref PubMed Scopus (734) Google Scholar, Kretschmer et al., 2010Kretschmer D. Gleske A. Rautenberg M. Wang R. Köberle M. Bohn E. Schönenberg T. Rabiet M. Boulay F. Klebanoff S.J. et al.Cell Host Microbe. 2010; 7 (this issue): 463-473Abstract Full Text Full Text PDF PubMed Scopus (188) Google Scholar). However, these cells are unable to destroy the invading S. aureus and eradicate the infection because of the other edge to this PSM sword, namely a powerful cytolytic activity that can destroy those incoming immune cells. Associated with this activity is extensive tissue destruction, which is presumably advantageous to S. aureus. These interesting findings need to be viewed in a wider context of recognition of S. aureus by the immune system. The human host employs an array of sensor mechanisms in order to recognize a spectrum of bacterial components. In addition to being recognized by formyl peptide receptors, PSMs (albeit from Staphylococcus epidermidis) have been reported to activate human cells through Toll-like receptors 2 (Hajjar et al., 2001Hajjar A.M. O'Mahony D.S. Ozinsky A. Underhill D.M. Aderem A. Klebanoff S.J. Wilson C.B. J. Immunol. 2001; 166: 15-19PubMed Google Scholar). It thus seems possible that the pathogen manipulates multiple host cell signaling pathways with a single molecule to mediate CA-MRSA disease. It is through such understanding of the dynamics of host-pathogen interactions that we may be able to develop novel strategies for intervention and treatment of debilitating bacterial diseases such as CA-MRSA. Human Formyl Peptide Receptor 2 Senses Highly Pathogenic Staphylococcus aureusKretschmer et al.Cell Host & MicrobeJune 17, 2010In BriefVirulence of emerging community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) and other highly pathogenic S. aureus strains depends on their production of phenol-soluble modulin (PSM) peptide toxins, which combine the capacities to attract and lyse neutrophils. The molecular basis of PSM-stimulated neutrophil recruitment has remained unclear. Here, we demonstrate that the human formyl peptide receptor 2 (FPR2/ALX), which has previously been implicated in control of endogenous inflammatory processes, senses PSMs at nanomolar concentrations and initiates proinflammatory neutrophil responses to CA-MRSA. Full-Text PDF Open Archive" @default.
• W2040284417 created "2016-06-24" @default.
• W2040284417 creator A5068817371 @default.
• W2040284417 date "2010-06-01" @default.
• W2040284417 modified "2023-10-16" @default.
• W2040284417 title "Phenol-Soluble Modulins of Staphylococcus aureus Lure Neutrophils into Battle" @default.
• W2040284417 cites W1925757606 @default.
• W2040284417 cites W1952842430 @default.
• W2040284417 cites W1958470604 @default.
• W2040284417 cites W1967715728 @default.
• W2040284417 cites W2013424910 @default.
• W2040284417 cites W2017618879 @default.
• W2040284417 cites W2038136893 @default.
• W2040284417 cites W2044750677 @default.
• W2040284417 cites W2101291779 @default.
• W2040284417 cites W2119768770 @default.
• W2040284417 doi "https://doi.org/10.1016/j.chom.2010.05.015" @default.
• W2040284417 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/20542245" @default.
• W2040284417 hasPublicationYear "2010" @default.
• W2040284417 type Work @default.
• W2040284417 sameAs 2040284417 @default.
• W2040284417 citedByCount "12" @default.
• W2040284417 countsByYear W20402844172012 @default.
• W2040284417 countsByYear W20402844172013 @default.
• W2040284417 countsByYear W20402844172014 @default.
• W2040284417 countsByYear W20402844172015 @default.
• W2040284417 countsByYear W20402844172019 @default.
• W2040284417 countsByYear W20402844172020 @default.
• W2040284417 countsByYear W20402844172023 @default.
• W2040284417 crossrefType "journal-article" @default.
• W2040284417 hasAuthorship W2040284417A5068817371 @default.
• W2040284417 hasBestOaLocation W20402844171 @default.
• W2040284417 hasConcept C166957645 @default.
• W2040284417 hasConcept C178790620 @default.
• W2040284417 hasConcept C185592680 @default.
• W2040284417 hasConcept C2777702071 @default.
• W2040284417 hasConcept C2778627824 @default.
• W2040284417 hasConcept C2779489039 @default.
• W2040284417 hasConcept C523546767 @default.
• W2040284417 hasConcept C54355233 @default.
• W2040284417 hasConcept C86803240 @default.
• W2040284417 hasConcept C89423630 @default.
• W2040284417 hasConcept C95457728 @default.
• W2040284417 hasConceptScore W2040284417C166957645 @default.
• W2040284417 hasConceptScore W2040284417C178790620 @default.
• W2040284417 hasConceptScore W2040284417C185592680 @default.
• W2040284417 hasConceptScore W2040284417C2777702071 @default.
• W2040284417 hasConceptScore W2040284417C2778627824 @default.
• W2040284417 hasConceptScore W2040284417C2779489039 @default.
• W2040284417 hasConceptScore W2040284417C523546767 @default.
• W2040284417 hasConceptScore W2040284417C54355233 @default.
• W2040284417 hasConceptScore W2040284417C86803240 @default.
• W2040284417 hasConceptScore W2040284417C89423630 @default.
• W2040284417 hasConceptScore W2040284417C95457728 @default.
• W2040284417 hasIssue "6" @default.
• W2040284417 hasLocation W20402844171 @default.
• W2040284417 hasLocation W20402844172 @default.
• W2040284417 hasOpenAccess W2040284417 @default.
• W2040284417 hasPrimaryLocation W20402844171 @default.
• W2040284417 hasRelatedWork W1558737772 @default.
• W2040284417 hasRelatedWork W2000391299 @default.
• W2040284417 hasRelatedWork W2003237632 @default.
• W2040284417 hasRelatedWork W2082480737 @default.
• W2040284417 hasRelatedWork W2348097125 @default.
• W2040284417 hasRelatedWork W2350977361 @default.
• W2040284417 hasRelatedWork W2357456606 @default.
• W2040284417 hasRelatedWork W2994023542 @default.
• W2040284417 hasRelatedWork W2999081595 @default.
• W2040284417 hasRelatedWork W3131868133 @default.
• W2040284417 hasVolume "7" @default.
• W2040284417 isParatext "false" @default.
• W2040284417 isRetracted "false" @default.
• W2040284417 magId "2040284417" @default.
• W2040284417 workType "article" @default.