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

Emerg Microbes Infect. 2023 Dec;12(2):2276335. doi: 10.1080/22221751.2023.2276335. Epub 2023 Nov 8.

Abstract

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.

Keywords: Diabetes; SaeRS two-component system; Staphylococcus aureus; colonization; microbiome.

MeSH terms

  • Animals
  • Diabetes Mellitus, Experimental* / complications
  • Diabetic Foot*
  • Humans
  • Methicillin-Resistant Staphylococcus aureus*
  • Mice
  • Nasal Cavity
  • Nose
  • Staphylococcal Infections*
  • Staphylococcus aureus

Grants and funding

This study was supported by the Innovative Research Team of High-Level Local Universities in Shanghai [grant number SHSMU-ZDCX20212200] to Q.L., National Natural Science Foundation of China [grant number 82072235] to Q.L., Shuguang Program supported by the Shanghai Education Development Foundation and Shanghai Municipal Education Commission [grant number 21SG17] to Q.L., Shanghai Sailing Program [grant number 22YF1438400] to Y.D.