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Diabetic foot infections are a common complication of diabetes.  Staphylococcus aureus  is frequently isolated from diabetic foot infections and commonly colonizes human nares. According to the study, the nasal microbiome analysis revealed that diabetic patients had a significantly altered nasal microbial composition and diversity. Typically, the fasting blood glucose (FBG) level had an impact on the abundance and sequence type (ST) of  S. aureus  in diabetic patients. We observed that highly virulent  S. aureus  ST7 strains were more frequently colonized in diabetic patients, especially those with poorly controlled FBG, while ST59 was dominant in healthy individuals.  S. aureus  ST7 strains were more resistant to human antimicrobial peptides and formed stronger biofilms than ST59 strains. Critically,  S. aureus  ST7 strains displayed higher virulence compared to ST59 strains  in vivo . The dominance of  S. aureus  ST7 strains in hyperglycemic environment is due to the higher activity of the SaeRS two-component system (TCS).  S. aureus  ST7 strains outcompeted ST59 both  in vitro , and in nasal colonization model in diabetic mice, which was abolished by the deletion of the SaeRS TCS. Our data indicated that highly virulent  S. aureus  strains preferentially colonize diabetic patients with poorly controlled FBG through SaeRS TCS. Detection of  S. aureus  colonization and elimination of colonizing  S. aureus  are critical in the care of diabetic patients with high FBG.

Diabetes mellitus promotes the nasal colonization of high virulent Staphylococcus aureus through the regulation of SaeRS two-component system