The global regulatory role of RsbUVW in virulence and biofilm formation in MRSA

The widespread prevalence of methicillin-resistant Staphylococcus aureus (MRSA) has caused serious challenges to clinical treatment. This study was designed to explore effective targets for MRSA prevention and control. The key virulence regulator was screened through the correlation analysis between virulence and various regulatory factors in the main clinical epidemic MRSA. The potential key factors were inactivated to further evaluate the inhibitory effect on the virulence of MRSA standard strain S. aureus ATCC43300 and its influence on drug resistance and biofilm formation. Enterobacterial repetitive intergenic consensus-PCR was used to analyze the clinical epidemic genotypes of MRSA. The virulence of MRSA was evaluated mainly by measuring its adhesion and invasion ability to A549 cells, the lethality to Galleria mellonella larvae, and the transcription level of related genes. The biofilm formation was assessed by crystal violet staining on polystyrene microplates. The results showed that most virulence factors of clinical representative MRSA strain were significantly positively correlated with RsbUVW system. After knocking out the rsbV gene, a key component of the rsbUVW system, the virulence of S. aureus ATCC43300 was significantly reduced (P < 0.05), as indicated by a significant decrease in lethality against G. mellonella larvae and invasion against A549 cells, and a significant decrease in the expression of immune escape related virulence factors polysaccharide intercellular adhesin (PIA) and staphyloxanthin. The biomass and stability of protein-dependent biofilm by S. aureus ATCC43300 were significantly increased. This study will provide useful information for the effective prevention and control of MRSA.