Comparative proteomic profiling of Streptococcus agalactiae recovered from the kidneys of diabetic mice

Streptococcus agalactiae is a significant opportunistic pathogen causing severe infections, including urinary tract infections and pyelonephritis in diabetic individuals. To explore the molecular mechanisms behind this susceptibility, we used a streptozotocin-induced diabetic murine model to evaluate S. agalactiae renal infection and performed the first comparative proteomic analysis of S. agalactiae COH1 isolates recovered from the kidneys of diabetic and non-diabetic mice. Diabetic mice exhibited significantly higher bacterial loads and more severe renal histopathological damage. Comparative proteomic profiling identified 2 751 proteins, with 82 significantly upregulated and 91 downregulated proteins in S. agalactiae COH1 isolate recovered from the kidneys of diabetic animals. Upregulated virulence factors included serine-rich repeat 2, type VII secretion, BibA, C5a peptidase, and PI-1. Functional analysis revealed a metabolic shift toward increased glycolysis, PTS system activity, and translation machinery, suggesting that the hyperglycemia promoted bacterial proliferation and energy production. Conversely, proteins related to proteolysis were downregulated. Our findings demonstrated that hyperglycemia induced a metabolic reprogramming and enhanced the expression of virulence-associated proteins in S. agalactiae. These adaptations contributed to increased colonization and tissue damage in diabetic kidney, providing potential molecular targets for future therapeutic interventions.