Nitrate Reductase NarGHJI Modulates Virulence via Regulation of Expression in Methicillin-Resistant Strain USA300 LAC.

Staphylococcus aureus is a pathogenic bacterium with a widespread distribution that can cause diverse severe diseases. The membrane-bound nitrate reductase NarGHJI serves respiratory function. However, little is known about its contribution to virulence. In this study, we demonstrated that disruption results in the downregulation of virulence genes (e.g., , , , , and ) and reduces the hemolytic activity of the methicillin-resistant S. aureus (MRSA) strain USA300 LAC. Moreover, we provided evidence that NarGHJI participates in regulating host inflammatory response. A mouse model of subcutaneous abscess and Galleria mellonella survival assay demonstrated that the mutant was significantly less virulent than the wild type. Interestingly, NarGHJI contributes to virulence in an -dependent manner, and the role of NarGHJI differs between different S. aureus strains. Our study highlights the novel role of NarGHJI in regulating virulence, thereby providing a new theoretical reference for the prevention and control of S. aureus infection. Staphylococcus aureus is a notorious pathogen that poses a great threat to human health. The emergence of drug-resistant strains has significantly increased the difficulty of preventing and treating S. aureus infection and enhanced the pathogenic ability of the bacterium. This indicates the importance of identifying novel pathogenic factors and revealing the regulatory mechanisms through which they regulate virulence. The nitrate reductase NarGHJI is mainly involved in bacterial respiration and denitrification, which can enhance bacterial survival. We demonstrated that disruption results in the downregulation of the system and -dependent virulence genes, suggesting that NarGHJI participates in the regulation of S. aureus virulence in an -dependent manner. Moreover, the regulatory approach is strain specific. This study provides a new theoretical reference for the prevention and control of S. aureus infection and reveals new targets for the development of therapeutic drugs.