Nitric oxide is a host cue for Salmonella Typhimurium systemic infection in mice.
Lingyan JiangWanwu LiXi HouShuai MaXinyue WangXiaolin YanBin YangDi HuangBin LiuLu FengPublished in: Communications biology (2023)
Nitric oxide (NO) is produced as an innate immune response against microbial infections. Salmonella Typhimurium (S. Typhimurium), the major causative pathogen of human gastroenteritis, induces more severe systemic disease in mice. However, host factors contributing to the difference in species-related virulence are unknown. Here, we report that host NO production promotes S. Typhimurium replication in mouse macrophages at the early infection stage by activating Salmonella pathogenicity island-2 (SPI-2). The NO signaling-induced SPI-2 activation is mediated by Fnr and PhoP/Q two-component system. NO significantly induced fnr transcription, while Fnr directly activated phoP/Q transcription. Mouse infection assays revealed a NO-dependent increase in bacterial burden in systemic organs during the initial days of infection, indicating an early contribution of host NO to virulence. This study reveals a host signaling-mediated virulence activation pathway in S. Typhimurium that contributes significantly to its systemic infection in mice, providing further insights into Salmonella pathogenesis and host-pathogen interaction.
Keyphrases
- listeria monocytogenes
- escherichia coli
- nitric oxide
- staphylococcus aureus
- pseudomonas aeruginosa
- biofilm formation
- drug induced
- endothelial cells
- high glucose
- high fat diet induced
- metabolic syndrome
- microbial community
- antimicrobial resistance
- early onset
- transcription factor
- signaling pathway
- high throughput
- oxidative stress
- wild type