Group B adaptation promotes survival in a hyperinflammatory diabetic wound environment.

Diabetic wounds have poor healing outcomes due to the presence of numerous pathogens and a dysregulated immune response. Group B (GBS) is commonly isolated from diabetic wound infections, but the mechanisms of GBS virulence during these infections have not been investigated. Here, we develop a murine model of GBS diabetic wound infection and, using dual RNA sequencing, demonstrate that GBS infection triggers an inflammatory response. GBS adapts to this hyperinflammatory environment by up-regulating virulence factors including those known to be regulated by the two-component system , such as the surface protein , and the operon, which is responsible for hemolysin/pigmentation production. We recover hyperpigmented/hemolytic GBS colonies from the murine diabetic wound, which we determined encode mutations in . We further demonstrate that GBS mutants in and are attenuated in the diabetic wound. This foundational study provides insight into the pathogenesis of GBS diabetic wound infections.