TY - JOUR T1 - Group B Streptococcus Adaptation Promotes Survival in a Hyperinflammatory Diabetic Wound Environment JF - bioRxiv DO - 10.1101/2022.06.27.497804 SP - 2022.06.27.497804 AU - Rebecca A. Keogh AU - Amanda L. Haeberle AU - Christophe J. Langouƫt-AstriƩ AU - Jeffrey S. Kavanaugh AU - Eric P. Schmidt AU - Garrett D. Moore AU - Alexander R. Horswill AU - Kelly S. Doran Y1 - 2022/01/01 UR - http://biorxiv.org/content/early/2022/09/26/2022.06.27.497804.abstract N2 - Diabetic wounds have poor healing outcomes due to the presence of numerous pathogens and a dysregulated immune response. Group B Streptococcus (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 upregulating virulence factors including those known to be regulated by the two-component system covRS, such as the surface protein pbsP, and the cyl 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 covR. We further demonstrate that GBS mutants in cylE and pbsP are attenuated in the diabetic wound. This foundational study provides insight into the pathogenesis of GBS diabetic wound infections.Teaser The Fight for Survival by the Bacterium Group B Streptococcus in the Diabetic Wound.Competing Interest StatementThe authors have declared no competing interest. ER -