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

Abstract

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 up-regulating 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.

Virulence characteristics of Gram-positive bacteria isolated from diabetic foot ulcers

“…1B , C ). We therefore chose to characterize E. faecalis, S. aureus and GBS strains moving forward as each of these species has been implicated in diabetic wound infection (Citron et al 2007 , ALbeloushi et al 2019 , Kalan et al 2019 , Keogh et al 2022 ).…”

“…Due to the high co-incidence of E. faecalis and GBS recovered with S. aureus in diabetic wound tissues, we sought to determine the consequence of polymicrobial infection in vivo . We utilized a murine excision wound model first described by Chong et al for E. faecalis chronic wound infection and induced diabetes in mice via low-dose streptozotocin injections as previously described (Chong et al 2017 , Keogh et al 2022 , Akbari et al 2023 ). Diabetic mice were wounded and infected with either S. aureus (LAC), E. faecalis , (OG1RF) or GBS (A909) alone, or co-infected with S. aureus .…”

“…Mice with glucose levels exceeding 200 mg/dL via glucometer were considered diabetic. Following, we utilized a murine model of chronic wound infection developed by Chong et al (Chong et al 2017 ) that we adapted for GBS infection (Keogh et al 2022 , Akbari et al 2023 ). Briefly, mice were anesthetized with 3% isofluorane and the dorsal area was shaved before treatment with Nair to completely remove hair.…”

The impact of nutritional immunity on Group B streptococcal pathogenesis during wound infection

“…1A ) ( 1 ). Mice were wounded with a 6-mm biopsy punch and infected with GBS strains A909 (serotype Ia) or CJB111 (serotype V) ( 2 ). These strains represent the two most common serotypes to cause invasive disease in non-pregnant adults and are commonly isolated from diabetic wounds ( 2 - 5 ).…”

“…Mice were wounded with a 6-mm biopsy punch and infected with GBS strains A909 (serotype Ia) or CJB111 (serotype V) ( 2 ). These strains represent the two most common serotypes to cause invasive disease in non-pregnant adults and are commonly isolated from diabetic wounds ( 2 - 5 ). Diabetic (Db) mice lost more weight, had larger wounds, and had increased bacterial burden in wound tissue regardless of GBS strain compared to non-diabetic (nDb) mice ( Fig.…”