Host Nitric Oxide Disrupts Microbial Cell-to-Cell Communication to Inhibit Staphylococcal Virulence.

摘要: Summary Staphylococcus aureus is a commensal bacterium that can asymptomatically colonize its host but also causes invasive infections. Quorum sensing regulates S. aureus virulence and the transition from to pathogenic organism. However, little known about how innate immunity affects interbacterial communication. We show nitric oxide suppresses staphylococcal by targeting Agr quorum system. Nitric oxide-mediated inhibition occurs through direct modification of cysteine residues C55, C123, C199 AgrA transcription factor. Cysteine decreases promoter occupancy as well agr operon sensing-activated toxin genes. In pneumonia model, mice lacking inducible oxide synthase develop more severe disease with heightened mortality proinflammatory cytokine responses. addition, α-toxin production increases in absence or oxide-sensitive residues. Our findings demonstrate an anti-virulence mechanism for immunity.