{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T17:00:35Z","timestamp":1792515635955,"version":"4.5.0"},"reference-count":70,"publisher":"American Society for Microbiology","issue":"8","license":[{"start":{"date-parts":[[2014,8,1]],"date-time":"2014-08-01T00:00:00Z","timestamp":1406851200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Infect Immun"],"published-print":{"date-parts":[[2014,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            <jats:named-content content-type=\"genus-species\">Staphylococcus aureus<\/jats:named-content>\n            is a leading cause of human bacterial infection, causing a wide spectrum of disease ranging from skin and soft tissue infections to life-threatening pneumonia and sepsis.\n            <jats:named-content content-type=\"genus-species\">S. aureus<\/jats:named-content>\n            toxins play an essential role in disease pathogenesis, contributing to both immunomodulation and host tissue injury. Prominent among these toxins are the membrane-active pore-forming cytolysin alpha-toxin (Hla) and the amphipathic \u03b1-helical phenol-soluble modulin (PSM) peptides. As deletion of either the\n            <jats:italic>hla<\/jats:italic>\n            or\n            <jats:italic>psm<\/jats:italic>\n            locus leads to a phenotypically similar virulence defect in skin and soft tissue infection, we sought to determine the relative contribution of each locus to disease pathogenesis. Here we show that production of Hla can be modulated by PSM expression. An\n            <jats:named-content content-type=\"genus-species\">S. aureus<\/jats:named-content>\n            mutant lacking PSM expression exhibits a transcriptional delay in\n            <jats:italic>hla<\/jats:italic>\n            mRNA production and therefore fails to secrete normal levels of Hla at early phases of growth. This leads to attenuation of virulence\n            <jats:italic>in vitro<\/jats:italic>\n            and in murine skin and lung models of infection, correlating with reduced recovery of Hla from host tissues. Production of Hla and restoration of staphylococcal virulence can be achieved in the\n            <jats:italic>psm<\/jats:italic>\n            mutant by plasmid-driven overexpression of\n            <jats:italic>hla<\/jats:italic>\n            . Our study suggests the coordinated action of Hla and PSMs in host tissue during early pathogenesis, confirming a major role for Hla in epithelial injury during\n            <jats:named-content content-type=\"genus-species\">S. aureus<\/jats:named-content>\n            infection. These findings highlight the possibility that therapeutics targeting PSM production may simultaneously prevent Hla-mediated tissue injury.\n          <\/jats:p>","DOI":"10.1128\/iai.00089-14","type":"journal-article","created":{"date-parts":[[2014,5,28]],"date-time":"2014-05-28T06:43:50Z","timestamp":1401259430000},"page":"3350-3358","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":58,"title":["The\n            <i>psm<\/i>\n            \u03b1 Locus Regulates Production of Staphylococcus aureus Alpha-Toxin during Infection"],"prefix":"10.1128","volume":"82","author":[{"given":"Bryan J.","family":"Berube","sequence":"first","affiliation":[{"name":"Department of Microbiology, University of Chicago, Chicago, Illinois, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Georgia R.","family":"Sampedro","sequence":"additional","affiliation":[{"name":"Department of Microbiology, University of Chicago, Chicago, Illinois, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Otto","sequence":"additional","affiliation":[{"name":"Laboratory of Human Bacterial Pathogenesis, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juliane","family":"Bubeck Wardenburg","sequence":"additional","affiliation":[{"name":"Department of Microbiology, University of Chicago, Chicago, Illinois, USA"},{"name":"Department of Pediatrics, University of Chicago, Chicago, Illinois, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1086\/522186"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199808203390806"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.298.15.1763"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.00081-09"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(09)61999-1"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-0691.2012.03914.x"},{"key":"e_1_3_3_8_2","volume-title":"Antibiotic resistance threats in the United States","author":"CDC","year":"2013","unstructured":"CDC. 2013. 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