The Staphylococcal Toxin Panton-Valentine Leukocidin Targets Human C5a Receptors
Panton-Valentine Leukocidin (PVL) is a staphylococcal bicomponent pore-forming toxin linked to severe invasive infections. Target-cell and species specificity of PVL are poorly understood, and the mechanism of action of this toxin in Staphylococcus aureus virulence is controversial. Here, we identif...
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| Veröffentlicht in: | Cell host & microbe 2013-05, Vol.13 (5), p.584-594 |
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| creator | Spaan, András N. Henry, Thomas van Rooijen, Willemien J.M. Perret, Magali Badiou, Cédric Aerts, Piet C. Kemmink, Johan de Haas, Carla J.C. van Kessel, Kok P.M. Vandenesch, François Lina, Gérard van Strijp, Jos A.G. |
| description | Panton-Valentine Leukocidin (PVL) is a staphylococcal bicomponent pore-forming toxin linked to severe invasive infections. Target-cell and species specificity of PVL are poorly understood, and the mechanism of action of this toxin in Staphylococcus aureus virulence is controversial. Here, we identify the human complement receptors C5aR and C5L2 as host targets of PVL, mediating both toxin binding and cytotoxicity. Expression and interspecies variations of the C5aR determine cell and species specificity of PVL. The C5aR binding PVL component, LukS-PV, is a potent inhibitor of C5a-induced immune cell activation. These findings provide insight into leukocidin function and staphylococcal virulence and offer directions for future investigations into individual susceptibility to severe staphylococcal disease.
•Staphylococcal Panton-Valentine leukocidin (PVL) targets complement receptors C5aR and C5L2•The C5aR is the major PVL receptor•The PVL component LukS-PV is a potent inhibitor of C5a-induced immune cell activation•C5aR expression levels and interspecies variations determine PVL target specificity |
| doi_str_mv | 10.1016/j.chom.2013.04.006 |
| format | Article |
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•Staphylococcal Panton-Valentine leukocidin (PVL) targets complement receptors C5aR and C5L2•The C5aR is the major PVL receptor•The PVL component LukS-PV is a potent inhibitor of C5a-induced immune cell activation•C5aR expression levels and interspecies variations determine PVL target specificity</description><identifier>ISSN: 1931-3128</identifier><identifier>EISSN: 1934-6069</identifier><identifier>DOI: 10.1016/j.chom.2013.04.006</identifier><identifier>PMID: 23684309</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Bacterial Proteins ; Bacterial Proteins - metabolism ; Bacterial Toxins ; Bacterial Toxins - metabolism ; Bacterial Toxins - toxicity ; Cells, Cultured ; Exotoxins ; Exotoxins - metabolism ; Exotoxins - toxicity ; Host-Pathogen Interactions ; Humans ; Leukocidins ; Leukocidins - metabolism ; Leukocidins - toxicity ; Life Sciences ; Receptor, Anaphylatoxin C5a ; Receptor, Anaphylatoxin C5a - metabolism ; Receptors, Chemokine ; Receptors, Chemokine - metabolism ; Staphylococcus aureus ; Staphylococcus aureus - immunology ; Staphylococcus aureus - pathogenicity</subject><ispartof>Cell host & microbe, 2013-05, Vol.13 (5), p.584-594</ispartof><rights>2013 Elsevier Inc.</rights><rights>Copyright © 2013 Elsevier Inc. All rights reserved.</rights><rights>Distributed under a Creative Commons Attribution 4.0 International License</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c500t-5874fbb1ab115fcd2d426136879edeb6859cc7e36ed40229d15fd859800c9453</citedby><cites>FETCH-LOGICAL-c500t-5874fbb1ab115fcd2d426136879edeb6859cc7e36ed40229d15fd859800c9453</cites><orcidid>0000-0002-0687-8565 ; 0000-0001-9412-7106 ; 0000-0002-9236-7998</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.chom.2013.04.006$$EHTML$$P50$$Gelsevier$$Hfree_for_read</linktohtml><link.rule.ids>230,315,781,785,886,3551,27929,27930,46000</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23684309$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://hal.science/hal-00965031$$DView record in HAL$$Hfree_for_read</backlink></links><search><creatorcontrib>Spaan, András N.</creatorcontrib><creatorcontrib>Henry, Thomas</creatorcontrib><creatorcontrib>van Rooijen, Willemien J.M.</creatorcontrib><creatorcontrib>Perret, Magali</creatorcontrib><creatorcontrib>Badiou, Cédric</creatorcontrib><creatorcontrib>Aerts, Piet C.</creatorcontrib><creatorcontrib>Kemmink, Johan</creatorcontrib><creatorcontrib>de Haas, Carla J.C.</creatorcontrib><creatorcontrib>van Kessel, Kok P.M.</creatorcontrib><creatorcontrib>Vandenesch, François</creatorcontrib><creatorcontrib>Lina, Gérard</creatorcontrib><creatorcontrib>van Strijp, Jos A.G.</creatorcontrib><title>The Staphylococcal Toxin Panton-Valentine Leukocidin Targets Human C5a Receptors</title><title>Cell host & microbe</title><addtitle>Cell Host Microbe</addtitle><description>Panton-Valentine Leukocidin (PVL) is a staphylococcal bicomponent pore-forming toxin linked to severe invasive infections. Target-cell and species specificity of PVL are poorly understood, and the mechanism of action of this toxin in Staphylococcus aureus virulence is controversial. Here, we identify the human complement receptors C5aR and C5L2 as host targets of PVL, mediating both toxin binding and cytotoxicity. Expression and interspecies variations of the C5aR determine cell and species specificity of PVL. The C5aR binding PVL component, LukS-PV, is a potent inhibitor of C5a-induced immune cell activation. These findings provide insight into leukocidin function and staphylococcal virulence and offer directions for future investigations into individual susceptibility to severe staphylococcal disease.
•Staphylococcal Panton-Valentine leukocidin (PVL) targets complement receptors C5aR and C5L2•The C5aR is the major PVL receptor•The PVL component LukS-PV is a potent inhibitor of C5a-induced immune cell activation•C5aR expression levels and interspecies variations determine PVL target specificity</description><subject>Bacterial Proteins</subject><subject>Bacterial Proteins - metabolism</subject><subject>Bacterial Toxins</subject><subject>Bacterial Toxins - metabolism</subject><subject>Bacterial Toxins - toxicity</subject><subject>Cells, Cultured</subject><subject>Exotoxins</subject><subject>Exotoxins - metabolism</subject><subject>Exotoxins - toxicity</subject><subject>Host-Pathogen Interactions</subject><subject>Humans</subject><subject>Leukocidins</subject><subject>Leukocidins - metabolism</subject><subject>Leukocidins - toxicity</subject><subject>Life Sciences</subject><subject>Receptor, Anaphylatoxin C5a</subject><subject>Receptor, Anaphylatoxin C5a - metabolism</subject><subject>Receptors, Chemokine</subject><subject>Receptors, Chemokine - metabolism</subject><subject>Staphylococcus aureus</subject><subject>Staphylococcus aureus - immunology</subject><subject>Staphylococcus aureus - pathogenicity</subject><issn>1931-3128</issn><issn>1934-6069</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kE1P3DAQhi3UCij0D3CociyHhHH8kUTiglbQrbQSqES9Wo49y3qbxIudoPLv6-1Sjj3NaPzMO9ZDyAWFggKVV9vCbPxQlEBZAbwAkEfklDaM5xJk8-FvT3NGy_qEfIpxCyAEVPSYnJRM1pxBc0oe2g1mj5PebV57b7wxus9a_9uN2YMeJz_mP3WP4-RGzFY4__LG2fTW6vCEU8yW86DHbCF09gMN7iYf4jn5uNZ9xM9v9Yy0d7ftYpmv7r99X9ysciMAplzUFV93HdUdpWJtbGl5KWn6VtWgxU7WojGmQibRcijLxibKpmENYBou2Bm5PMRudK92wQ06vCqvnVrerNR-BtBIAYy-0MR-PbC74J9njJMaXDTY93pEP0dFmWC8qoSoEloeUBN8jAHX79kU1F662qq9dLWXroCnMzItfXnLn7sB7fvKP8sJuD4AmIS8OAwqGoejQesCmklZ7_6X_wcK9pFP</recordid><startdate>20130515</startdate><enddate>20130515</enddate><creator>Spaan, András N.</creator><creator>Henry, Thomas</creator><creator>van Rooijen, Willemien J.M.</creator><creator>Perret, Magali</creator><creator>Badiou, Cédric</creator><creator>Aerts, Piet C.</creator><creator>Kemmink, Johan</creator><creator>de Haas, Carla J.C.</creator><creator>van Kessel, Kok P.M.</creator><creator>Vandenesch, François</creator><creator>Lina, Gérard</creator><creator>van Strijp, Jos A.G.</creator><general>Elsevier Inc</general><general>Elsevier</general><scope>6I.</scope><scope>AAFTH</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>1XC</scope><orcidid>https://orcid.org/0000-0002-0687-8565</orcidid><orcidid>https://orcid.org/0000-0001-9412-7106</orcidid><orcidid>https://orcid.org/0000-0002-9236-7998</orcidid></search><sort><creationdate>20130515</creationdate><title>The Staphylococcal Toxin Panton-Valentine Leukocidin Targets Human C5a Receptors</title><author>Spaan, András N. ; Henry, Thomas ; van Rooijen, Willemien J.M. ; Perret, Magali ; Badiou, Cédric ; Aerts, Piet C. ; Kemmink, Johan ; de Haas, Carla J.C. ; van Kessel, Kok P.M. ; Vandenesch, François ; Lina, Gérard ; van Strijp, Jos A.G.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c500t-5874fbb1ab115fcd2d426136879edeb6859cc7e36ed40229d15fd859800c9453</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Bacterial Proteins</topic><topic>Bacterial Proteins - metabolism</topic><topic>Bacterial Toxins</topic><topic>Bacterial Toxins - metabolism</topic><topic>Bacterial Toxins - toxicity</topic><topic>Cells, Cultured</topic><topic>Exotoxins</topic><topic>Exotoxins - metabolism</topic><topic>Exotoxins - toxicity</topic><topic>Host-Pathogen Interactions</topic><topic>Humans</topic><topic>Leukocidins</topic><topic>Leukocidins - metabolism</topic><topic>Leukocidins - toxicity</topic><topic>Life Sciences</topic><topic>Receptor, Anaphylatoxin C5a</topic><topic>Receptor, Anaphylatoxin C5a - metabolism</topic><topic>Receptors, Chemokine</topic><topic>Receptors, Chemokine - metabolism</topic><topic>Staphylococcus aureus</topic><topic>Staphylococcus aureus - immunology</topic><topic>Staphylococcus aureus - pathogenicity</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Spaan, András N.</creatorcontrib><creatorcontrib>Henry, Thomas</creatorcontrib><creatorcontrib>van Rooijen, Willemien J.M.</creatorcontrib><creatorcontrib>Perret, Magali</creatorcontrib><creatorcontrib>Badiou, Cédric</creatorcontrib><creatorcontrib>Aerts, Piet C.</creatorcontrib><creatorcontrib>Kemmink, Johan</creatorcontrib><creatorcontrib>de Haas, Carla J.C.</creatorcontrib><creatorcontrib>van Kessel, Kok P.M.</creatorcontrib><creatorcontrib>Vandenesch, François</creatorcontrib><creatorcontrib>Lina, Gérard</creatorcontrib><creatorcontrib>van Strijp, Jos A.G.</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>Hyper Article en Ligne (HAL)</collection><jtitle>Cell host & microbe</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Spaan, András N.</au><au>Henry, Thomas</au><au>van Rooijen, Willemien J.M.</au><au>Perret, Magali</au><au>Badiou, Cédric</au><au>Aerts, Piet C.</au><au>Kemmink, Johan</au><au>de Haas, Carla J.C.</au><au>van Kessel, Kok P.M.</au><au>Vandenesch, François</au><au>Lina, Gérard</au><au>van Strijp, Jos A.G.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The Staphylococcal Toxin Panton-Valentine Leukocidin Targets Human C5a Receptors</atitle><jtitle>Cell host & microbe</jtitle><addtitle>Cell Host Microbe</addtitle><date>2013-05-15</date><risdate>2013</risdate><volume>13</volume><issue>5</issue><spage>584</spage><epage>594</epage><pages>584-594</pages><issn>1931-3128</issn><eissn>1934-6069</eissn><abstract>Panton-Valentine Leukocidin (PVL) is a staphylococcal bicomponent pore-forming toxin linked to severe invasive infections. Target-cell and species specificity of PVL are poorly understood, and the mechanism of action of this toxin in Staphylococcus aureus virulence is controversial. Here, we identify the human complement receptors C5aR and C5L2 as host targets of PVL, mediating both toxin binding and cytotoxicity. Expression and interspecies variations of the C5aR determine cell and species specificity of PVL. The C5aR binding PVL component, LukS-PV, is a potent inhibitor of C5a-induced immune cell activation. These findings provide insight into leukocidin function and staphylococcal virulence and offer directions for future investigations into individual susceptibility to severe staphylococcal disease.
•Staphylococcal Panton-Valentine leukocidin (PVL) targets complement receptors C5aR and C5L2•The C5aR is the major PVL receptor•The PVL component LukS-PV is a potent inhibitor of C5a-induced immune cell activation•C5aR expression levels and interspecies variations determine PVL target specificity</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>23684309</pmid><doi>10.1016/j.chom.2013.04.006</doi><tpages>11</tpages><orcidid>https://orcid.org/0000-0002-0687-8565</orcidid><orcidid>https://orcid.org/0000-0001-9412-7106</orcidid><orcidid>https://orcid.org/0000-0002-9236-7998</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | Bacterial Proteins Bacterial Proteins - metabolism Bacterial Toxins Bacterial Toxins - metabolism Bacterial Toxins - toxicity Cells, Cultured Exotoxins Exotoxins - metabolism Exotoxins - toxicity Host-Pathogen Interactions Humans Leukocidins Leukocidins - metabolism Leukocidins - toxicity Life Sciences Receptor, Anaphylatoxin C5a Receptor, Anaphylatoxin C5a - metabolism Receptors, Chemokine Receptors, Chemokine - metabolism Staphylococcus aureus Staphylococcus aureus - immunology Staphylococcus aureus - pathogenicity |
| title | The Staphylococcal Toxin Panton-Valentine Leukocidin Targets Human C5a Receptors |
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