{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T13:29:06Z","timestamp":1787232546772,"version":"build-2736575974"},"reference-count":54,"publisher":"American Society for Microbiology","issue":"8","license":[{"start":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T00:00:00Z","timestamp":1787184000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T00:00:00Z","timestamp":1787184000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["PJT-183848"],"award-info":[{"award-number":["PJT-183848"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["J Bacteriol"],"published-print":{"date-parts":[[2026,8,20]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      <jats:italic toggle=\"yes\">Staphylococcus aureus<\/jats:italic>\n                      is a globally prevalent gram-positive pathogen that can cause numerous types of infection. Due to host nutritional immunity and iron (Fe) sequestration,\n                      <jats:italic toggle=\"yes\">S. aureus<\/jats:italic>\n                      experiences Fe limitation during infection. To overcome this,\n                      <jats:italic toggle=\"yes\">S. aureus<\/jats:italic>\n                      expresses an arsenal of Fe acquisition systems whose expression is coordinated through the Fe-binding transcriptional regulator, Fur. Here, from a screen to identify\n                      <jats:italic toggle=\"yes\">S. aureus<\/jats:italic>\n                      mutants defective for Fe-restricted growth, we identified several with mutations in\n                      <jats:italic toggle=\"yes\">perR<\/jats:italic>\n                      , encoding a transcriptional regulator involved in resistance to oxidative stress. RNA-seq identified that the most downregulated genes in a\n                      <jats:italic toggle=\"yes\">perR<\/jats:italic>\n                      mutant growing in Fe-restriction are those from the\n                      <jats:italic toggle=\"yes\">sbn<\/jats:italic>\n                      operon that encodes staphyloferrin B biosynthesis. In agreement,\n                      <jats:italic toggle=\"yes\">perR<\/jats:italic>\n                      mutants grew poorly in Fe-deficient media due to deficient staphyloferrin B production. In a subcutaneous model of\n                      <jats:italic toggle=\"yes\">S. aureus<\/jats:italic>\n                      skin infection,\n                      <jats:italic toggle=\"yes\">S. aureus perR<\/jats:italic>\n                      caused significantly smaller lesions, consistent with our finding that this mutant had decreased alpha-hemolysin expression during Fe-restricted growth. These findings are consistent with the hypothesis that PerR acts to fine-tune access to Fe ostensibly to avoid Fe-dependent toxicity. The importance of the PerR function to\n                      <jats:italic toggle=\"yes\">S. aureus<\/jats:italic>\n                      was further highlighted by examination of over 8,000 human bloodstream isolates of\n                      <jats:italic toggle=\"yes\">S. aureus<\/jats:italic>\n                      , showing that the PerR sequence was highly conserved. Together, these findings demonstrate the importance of PerR to\n                      <jats:italic toggle=\"yes\">S. aureus<\/jats:italic>\n                      in providing an additional level of regulation of Fe homeostasis beyond Fur-dependent Fe sensing.\n                    <\/jats:p>\n                    <jats:sec>\n                      <jats:title>IMPORTANCE<\/jats:title>\n                      <jats:p>\n                        <jats:italic toggle=\"yes\">Staphylococcus aureus<\/jats:italic>\n                        is a notoriously antibiotic-resistant human pathogen and has the potential to cause a myriad of potentially life-threatening infections. Understanding the intricacies of\n                        <jats:italic toggle=\"yes\">S. aureus<\/jats:italic>\n                        pathogenesis in the host will underpin the development of novel therapeutic approaches that target bacterial virulence mechanisms rather than essential cellular processes. The significance of our research lies in identifying how\n                        <jats:italic toggle=\"yes\">S. aureus<\/jats:italic>\n                        regulates Fe acquisition in response to environmental signals, providing further insight into nutrient sensing and acquisition at the host\u2013pathogen interface to facilitate the development of therapeutics that may target this process.\n                      <\/jats:p>\n                    <\/jats:sec>\n                  <\/jats:sec>","DOI":"10.1128\/jb.00149-26","type":"journal-article","created":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T16:31:09Z","timestamp":1784046669000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":0,"title":["The oxidative stress regulator, PerR, is required for staphyloferrin B-mediated iron acquisition in\n                    <i>Staphylococcus aureus<\/i>"],"prefix":"10.1128","volume":"208","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-0491-8452","authenticated-orcid":false,"given":"Alexander A.","family":"Sheikh","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02grkyz14","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Microbiology and Immunology, University of Western Ontario","place":["London, Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3263-2227","authenticated-orcid":true,"given":"Ronald S.","family":"Flannagan","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02grkyz14","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Microbiology and Immunology, University of Western Ontario","place":["London, Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathan 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