title: Salmonella proteomics under oxidative stress reveals coordinated regulation of antioxidant defense with iron metabolism and bacterial virulence.
abstract: 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 H2O2. 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 H2O2challenge. 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 H2O2treatment. 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.
authors.affiliation: Institute of Analytical Chemistry and Synthetic and Functional Biomolecules Center, College of Chemistry and Molecular Engineering, Peking University, 100871 Beijing, China.
authors.forename: Jiaqi
authors.initials: J
authors.lastname: Fu
authors.affiliation: Institute of Analytical Chemistry and Synthetic and Functional Biomolecules Center, College of Chemistry and Molecular Engineering, Peking University, 100871 Beijing, China.
authors.forename: Linlu
authors.initials: L
authors.lastname: Qi
authors.affiliation: Institute of Analytical Chemistry and Synthetic and Functional Biomolecules Center, College of Chemistry and Molecular Engineering, Peking University, 100871 Beijing, China.
authors.forename: Mo
authors.initials: M
authors.lastname: Hu
authors.affiliation: Institute of Analytical Chemistry and Synthetic and Functional Biomolecules Center, College of Chemistry and Molecular Engineering, Peking University, 100871 Beijing, China.
authors.forename: Yanhua
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Institute of Analytical Chemistry and Synthetic and Functional Biomolecules Center, College of Chemistry and Molecular Engineering, Peking University, 100871 Beijing, China.
authors.forename: Kaiwen
authors.initials: K
authors.lastname: Yu
authors.affiliation: State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, 100085 Beijing, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Liu
authors.affiliation: Institute of Analytical Chemistry and Synthetic and Functional Biomolecules Center, College of Chemistry and Molecular Engineering, Peking University, 100871 Beijing, China. Electronic address: xiaoyun.liu@pku.edu.cn.
authors.forename: Xiaoyun
authors.initials: X
authors.lastname: Liu
mesh_terms: D000975:Antioxidants / Q000378:metabolism*; D001426:Bacterial Proteins / Q000378:metabolism*; D006861:Hydrogen Peroxide / Q000494:pharmacology; D007501:Iron / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects; D040901:Proteomics; D012486:Salmonella typhimurium / Q000378:metabolism* / Q000472:pathogenicity; D037521:Virulence Factors / Q000378:metabolism*
chemical_list: D000975:Antioxidants; D001426:Bacterial Proteins; D037521:Virulence Factors; D006861:Hydrogen Peroxide; D007501:Iron
keywords: Antioxidant defense; Bacterial virulence; Iron metabolism; Oxidative stress; Salmonella proteomics