Abstract

Staphylococcus aureus is a major source of community and nosocomial infections. Due to the extensive application of antibiotics, S. aureus has developed resistance to antibiotics, especially vancomycin, making clinical treatment challenging. Staphylococcal accessory regulator A (SarA) modulates S. aureus virulence by regulating the principal virulence factors. However, its role in vancomycin resistance remains largely unknown. Herein, we found that SarA not only reduces the susceptibility of S. aureus to vancomycin by directly inhibiting the expression of autolysis-related genes, but also enhances resistance to vancomycin by negatively regulating the transcription of an ATP-binding cassette (ABC) transporter, ABC-like, thereby altering the bacterial surface charge and reducing vancomycin’s binding efficiency to the cell wall. Moreover, the regulation of antibiotic resistance by SarA is strain-dependent. Our study uncovers the roles of SarA in regulating vancomycin resistance, providing potential targets and ideas for the prevention and control of vancomycin-intermediate S. aureus infections.