VraSR has an important role in immune evasion of Staphylococcus aureus with low level vancomycin resistance

Abstract Vancomycin-intermediate Staphylococcus aureus (VISA) and heterogeneous VISA (hVISA) are increasingly being reported as associated with treatment failure. Previous studies indicated that VISA/hVISA resists clearance by the host immune system, thereby allowing persistence within the host. VraSR is a vancomycin-resistance-associated sensor/regulator that is highly expressed in VISA/hVISA strains. Whether VraSR plays an important role in immune escape by VISA/hVISA strains is unclear. Here, we constructed a vraSR deletion mutant strain (Δ vraSR ) and complementary strain (CΔ vraSR ) in Mu3 to investigate the effect of VraSR on S. aureus viability in polymorphonuclear leukocytes (PMNs). The Δ vraSR strain was more susceptible to phagocytosis by PMNs and reduced the ability of S. aureus to survive within PMNs. Δ vraSR showed phenotypic changes, including a thinner cell wall, reduced adhesion, and decreased biofilm-forming ability. Real-time quantitative PCR revealed that the transcript levels of cell wall synthesis-related genes ( cap5K , cap5N , nanA , tagA , murD ) and adhesion-associated genes ( fnbA , fnbB , clfA , ebps , sbi ) were significantly decreased in the Δ vraSR strain compared with Mu3. In summary, VraSR promotes the survival of S. aureus in the host, which may be associated with an increase in the thickness of the cell wall, adhesion, and biofilm formation.