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Community-associated methicillin-resistant<jats:named-content content-type=\"genus-species\">Staphylococcus aureus<\/jats:named-content>(CA-MRSA) strains such as USA300 cause particularly severe and difficult-to-treat cases of IAV-associated pneumonia. CA-MRSA strains are known to produce extraordinarily large amounts of phenol-soluble modulin (PSM) peptides, which are important cytotoxins and proinflammatory molecules that contribute to several types of<jats:named-content content-type=\"genus-species\">S. aureus<\/jats:named-content>infection. However, their potential role in pneumonia has remained elusive. We determined the impact of PSMs on human lung epithelial cells and found that PSMs are cytotoxic and induce the secretion of the proinflammatory cytokine interleukin-8 (IL-8) in these cells. Both effects were boosted by previous infection with the 2009 swine flu pandemic IAV H1N1 strain, suggesting that PSMs may contribute to lung inflammation and damage in IAV-associated<jats:named-content content-type=\"genus-species\">S. aureus<\/jats:named-content>pneumonia. Notably, the PSM-producing USA300 strain caused a higher mortality rate than did an isogenic PSM-deficient mutant in a mouse IAV-<jats:named-content content-type=\"genus-species\">S. aureus<\/jats:named-content>pneumonia coinfection model, indicating that PSMs are major virulence factors in IAV-associated<jats:named-content content-type=\"genus-species\">S. aureus<\/jats:named-content>pneumonia and may represent important targets for future anti-infective therapies.<\/jats:p>","DOI":"10.1128\/iai.00620-17","type":"journal-article","created":{"date-parts":[[2017,9,12]],"date-time":"2017-09-12T00:40:30Z","timestamp":1505176830000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":21,"title":["Phenol-Soluble Modulin Peptides Contribute to Influenza A Virus-Associated Staphylococcus aureus Pneumonia"],"prefix":"10.1128","volume":"85","author":[{"given":"Dominik Alexander","family":"Bloes","sequence":"first","affiliation":[{"name":"Interfaculty Institute of Microbiology and Infection Medicine, Infection Biology, University of T\u00fcbingen, T\u00fcbingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emanuel","family":"Haasbach","sequence":"additional","affiliation":[{"name":"Interfaculty Institute for Cell Biology, Immunology, T\u00fcbingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmen","family":"Hartmayer","sequence":"additional","affiliation":[{"name":"Interfaculty Institute for Cell Biology, Immunology, T\u00fcbingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tobias","family":"Hertlein","sequence":"additional","affiliation":[{"name":"Institute for Molecular Infection Biology, University of W\u00fcrzburg, W\u00fcrzburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karin","family":"Klingel","sequence":"additional","affiliation":[{"name":"Department of Molecular Pathology, Institute for Pathology and Neuropathology, University Hospital T\u00fcbingen, T\u00fcbingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dorothee","family":"Kretschmer","sequence":"additional","affiliation":[{"name":"Interfaculty Institute of Microbiology and Infection Medicine, Infection Biology, University of T\u00fcbingen, T\u00fcbingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oliver","family":"Planz","sequence":"additional","affiliation":[{"name":"Interfaculty Institute for Cell Biology, Immunology, T\u00fcbingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3209-8626","authenticated-orcid":false,"given":"Andreas","family":"Peschel","sequence":"additional","affiliation":[{"name":"Interfaculty Institute of Microbiology and Infection Medicine, Infection Biology, University of T\u00fcbingen, T\u00fcbingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(10)61459-6"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1165\/rcmb.2007-0417OC"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.02885-12"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.5858\/134.2.235"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.200909-1420OC"},{"key":"e_1_3_2_7_2","first-page":"1071","article-title":"Bacterial coinfections in lung tissue specimens from fatal cases of 2009 pandemic influenza A (H1N1)\u2014United States, May-August 2009","volume":"58","author":"Centers for Disease Control and Prevention","year":"2009","unstructured":"Centers for Disease Control and Prevention. 2009. 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