Endogenous nitric oxide promotes Staphylococcus aureus virulence by activating autophagy

作者：Nadira Nurxat, Qichen Wang, Na Zhao, Yanan Guo, Xilong Zhang, Yanan Wang, Ying Jian, Hua Wang, Shengbing Yang, Min Li, Qian Liu · 发表于：mBio · 年份：2025 · DOI：10.1128/mbio.04006-24 · 被引用次数：5 · 研究领域：Bacterial biofilms and quorum sensing、Neutrophil, Myeloperoxidase and Oxidative Mechanisms、Antimicrobial Resistance in Staphylococcus

ABSTRACT Endogenous nitric oxide (NO) is a small molecule that has been demonstrated to affect the physiology and survival of bacteria. The role of endogenous NO for Staphylococcus aureus survival inside host cells remains unclear. Here, we show that the production of endogenous NO by bacterial nitrate reductase (NR) is affected by molybdopterin biosynthesis protein A (MoeA), which is essential for molybdenum cofactor synthesis in S. aureus . During the infection, the production of endogenous NO promotes S. aureus survival inside macrophages by initiating cellular autophagy. Mechanistically, bacterial endogenous NO can modify the host regulatory protein thioredoxin vis S-nitrosylation, subsequently triggering the phosphorylation of the JNK-Bcl-2 pathway and promoting the initiation of autophagy through the release of Beclin1. Moreover, we confirmed the critical role of MoeA in bacterial survival in vivo by using bloodstream infection, pneumonia, and skin abscess model on both wild-type and autophagy-deficient mice. Interestingly, we observed the significantly increased production of NO and activation of cellular autophagy of sequence type (ST)5 compared with ST239, suggesting that the initiation of autophagy is involved in the clone shift of S. aureus . Our data offered new insights on the role of bacterial endogenous NO in regulating the host signal pathway during infection inside host cells. IMPORTANCE Understanding the mechanism underlying Staphylococcus aureus pathogenesi...