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The bacterium Group B\n                      <jats:italic toggle=\"yes\">Streptococcus<\/jats:italic>\n                      (GBS) is frequently isolated from diabetic wounds; however, little is known about how GBS adapts to survive in this niche. Previously, we found that GBS acquires stable mutations in the major two-component system CovRS during murine diabetic wound infection that result in increased pigmentation. Here, we further characterize these pigmented variants and determine the consequences on GBS survival. Using a murine model of wound infection, we find that\n                      <jats:italic toggle=\"yes\">covRS<\/jats:italic>\n                      mutants arise specifically in diabetic hosts and are selected for across multiple GBS backgrounds. Whole genome sequencing of pigmented isolates revealed mutations in both\n                      <jats:italic toggle=\"yes\">covR<\/jats:italic>\n                      and\n                      <jats:italic toggle=\"yes\">covS<\/jats:italic>\n                      , with most isolates having a single nucleotide insertion or deletion in the\n                      <jats:italic toggle=\"yes\">covR<\/jats:italic>\n                      promoter region. Phenotypic analysis of murine-acquired mutants reveals enhanced traits associated with virulence, including increased hemolytic activity, host cell cytotoxicity, and elevated nuclease activity. While our previous and current study indicated that engineered\n                      <jats:italic toggle=\"yes\">covR<\/jats:italic>\n                      deletion mutants do not exhibit increased survival in the diabetic wound, we observe that a pigmented isolate survived better than wild-type during co-infection with\n                      <jats:italic toggle=\"yes\">Enterococcus faecalis<\/jats:italic>\n                      , another frequently isolated wound pathogen. Finally, we find that depletion of neutrophils reduces the frequency of\n                      <jats:italic toggle=\"yes\">covRS<\/jats:italic>\n                      mutant variants that arise in the population. Our work highlights the emergence of\n                      <jats:italic toggle=\"yes\">covRS<\/jats:italic>\n                      mutations in GBS, and the consequences of these variations are associated with enhanced virulence and competitive fitness, underscoring the importance of these regulatory changes in the context of diabetic wounds.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1128\/iai.00099-26","type":"journal-article","created":{"date-parts":[[2026,6,15]],"date-time":"2026-06-15T12:01:36Z","timestamp":1781524896000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":0,"title":["The diabetic wound microenvironment drives emergence and maintenance of CovRS variants in group B\n                    <i>Streptococcus<\/i>"],"prefix":"10.1128","volume":"94","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8376-2307","authenticated-orcid":true,"given":"Rebecca 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