Fu Jiaqi, Qi Linlu, Hu Mo, Liu Yanhua, Yu Kaiwen, Liu Qian, Liu Xiaoyun
Institute of Analytical Chemistry and Synthetic and Functional Biomolecules Center, College of Chemistry and Molecular Engineering, Peking University, 100871 Beijing, China.
State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, 100085 Beijing, China.
J Proteomics. 2017 Mar 22;157:52-58. doi: 10.1016/j.jprot.2017.02.004. Epub 2017 Feb 11.
Salmonella Typhimurium is a bacterial pathogen that can cause widespread gastroenteritis. Salmonella encounters reactive oxygen species both under free-living conditions and within their mammalian host during infection. To study its response to oxidative stress, we performed the first large-scale proteomic profiling of Salmonella upon exposure to HO. Among 1600 detected proteins, 83 proteins showed significantly altered abundance. Interestingly, only a subset of known antioxidants was induced, likely due to distinct regulatory mechanisms. In addition, we found elevation of several Salmonella acquired phage products with potential contribution to DNA repair under oxidative stress. Furthermore, we observed robust induction of iron-uptake systems and disruption of these pathways led to bacterial survival defects under HO challenge. Importantly, this work is the first to report that oxidative stress severely repressed the Salmonella type III secretion system (T3SS), reducing its virulence. Biological significance Salmonella, a Gram-negative bacterial pathogen, encounters reactive oxygen species (ROS) both endogenously and exogenously. To better understand its response to oxidative stress, we performed the first large-scale profiling of Salmonella protein expression upon HO treatment. Among 1600 quantified proteins, the abundance of 116 proteins was altered significantly. Notably, iron acquisition systems were induced to promote bacterial survival under oxidative stress. Furthermore, we are the first to report that oxidative stress severely repressed Salmonella type III secretion system and hence reduced its virulence. We believe that these findings will not only help us better understand the molecular mechanisms that Salmonella has evolved to counteract ROS but also the global impact of oxidative stress on bacterial physiology.
鼠伤寒沙门氏菌是一种可引发广泛肠胃炎的细菌病原体。沙门氏菌在自由生活条件下以及感染期间在其哺乳动物宿主内都会遭遇活性氧。为了研究其对氧化应激的反应，我们首次对暴露于过氧化氢（HO）的沙门氏菌进行了大规模蛋白质组分析。在检测到的1600种蛋白质中，有83种蛋白质的丰度发生了显著变化。有趣的是，只有一部分已知的抗氧化剂被诱导产生，这可能是由于不同的调控机制所致。此外，我们发现几种沙门氏菌获得的噬菌体产物有所增加，这些产物可能在氧化应激下对DNA修复有贡献。此外，我们观察到铁摄取系统被强烈诱导，并且这些途径的破坏导致细菌在过氧化氢挑战下的生存缺陷。重要的是，这项工作首次报道氧化应激严重抑制沙门氏菌III型分泌系统（T3SS），降低其毒力。生物学意义：革兰氏阴性细菌病原体沙门氏菌在体内和体外都会遭遇活性氧（ROS）。为了更好地理解其对氧化应激的反应，我们首次对经过氧化氢处理的沙门氏菌蛋白质表达进行了大规模分析。在1600种定量蛋白质中，116种蛋白质的丰度发生了显著变化。值得注意的是，铁摄取系统被诱导以促进细菌在氧化应激下的生存。此外，我们首次报道氧化应激严重抑制沙门氏菌III型分泌系统，从而降低其毒力。我们相信这些发现不仅将帮助我们更好地理解沙门氏菌为对抗活性氧而进化出的分子机制，还将帮助我们理解氧化应激对细菌生理学的整体影响。
