Introduction: In recent years, multidrug-resistant methicillin-resistant Staphylococcus aureus  has become increasingly prevalent, which raised a huge challenge to antibiotic treatment of infectious diseases. The anti-virulence strategy targeting virulent factors is a promising novel therapy for S. aureus  infection. The virulence mechanism of S. aureus  was needed to explore deeply to develop more targets and improve the effectiveness of anti-virulence strategies.
Results: In this study, we found mraZ  was highly conserved in S. aureus , and its production is homologous with the MraZ of Escherichia coli , a transcriptional regulator involved in the growth and cell division of E. coli . To investigate the function of mraZ  in S. aureus , we constructed a MW2 mraZ  deletion mutant and its complementary mutant for virulence comparison. Although no remarkable influence on the growth, the mraZ  deletion mutant led to significantly reduced resistance to human neutrophils and decreased virulence in Galleria mellonella  model as well as mouse skin and soft tissue infection models, indicating its essential contribution to virulence and immune evasion to support the pathogenicity of S. aureus  infection. RNA-Seq and quantitative RT-qPCR revealed that MraZ is a multi-functional regulator; it involves in diverse biological processes and can up-regulate the expression of various virulence genes by agr  and sarA .
Conclusion: mraZ  plays vital roles in the pathyogenicity of S. aureus  via regulating many virulence genes. It may be an attractive target for anti-virulence therapy of S. aureus .
Keywords: Staphylococcus aureus , virulence, mraZ , agr , sarA