Functional Insights of MraZ on the Pathogenicity of Staphylococcus aureus

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.