title: Methionine sulfoxide reductase A (MsrA) contributes to Salmonella Typhimurium survival against oxidative attack of neutrophils.
abstract: Salmonella Typhimurium (ST) must evade neutrophil assault for infection establishment in the host. Myeloperoxidase generated HOCl is the key antimicrobial agent produced by the neutrophils; and methionine (Met) residues are the primary targets of this oxidant. Oxidation of Mets leads to methionine sulfoxide (Met-SO) formation and consequently compromises the protein function(s). Methionine sulfoxide reductase A (MsrA) reductively repairs Met-SO to Mets. In this manner, MsrA maintains the function(s) of key proteins which are important for virulence of ST and enhance the survival of this bacterium under oxidative stress. We constructed msrA gene deletion strain (ΔmsrA). The primers located in the flanking regions to ΔmsrA gene amplified 850 and 300 bp amplicons in ST and ΔmsrA strains, respectively. The ΔmsrA strain grew normally in in vitro broth culture. However, ΔmsrA strain showed high susceptibility (p<0.001) to very low concentrations of HOCl which was restored (at least in part) by plasmid based complementation. ΔmsrA strain was hypersensitive (than ST) to the granules isolated from neutrophils. Further, the ΔmsrA strain was significantly (p<0.05) more susceptible to neutrophil mediated killing.
authors.affiliation: The Immunology Section, Indian Veterinary Research Institute, Izatnagar, Uttar Pradesh 243 122, India.
authors.forename: Raj Narayan
authors.initials: RN
authors.lastname: Trivedi
authors.affiliation: Division of Biochemistry, Indian Veterinary Research Institute, Izatnagar, Uttar Pradesh 243 122, India.
authors.forename: Pranjali
authors.initials: P
authors.lastname: Agarwal
authors.affiliation: Division of Biochemistry, Indian Veterinary Research Institute, Izatnagar, Uttar Pradesh 243 122, India.
authors.forename: Manoj
authors.initials: M
authors.lastname: Kumawat
authors.affiliation: Division of Veterinary Public Health, Indian Veterinary Research Institute, Izatnagar, Uttar Pradesh 243 122, India.
authors.forename: Pavan Kumar
authors.initials: PK
authors.lastname: Pesingi
authors.affiliation: Animal Health Division, CIRG, Makhdoom, Mathura, India.
authors.forename: Vivek Kumar
authors.initials: VK
authors.lastname: Gupta
authors.affiliation: The Immunology Section, Indian Veterinary Research Institute, Izatnagar, Uttar Pradesh 243 122, India.
authors.forename: Tapas Kumar
authors.initials: TK
authors.lastname: Goswami
authors.affiliation: Division of Biochemistry, Indian Veterinary Research Institute, Izatnagar, Uttar Pradesh 243 122, India. Electronic address: manishbiochemistry@gmail.com.
authors.forename: Manish
authors.initials: M
authors.lastname: Mahawar
mesh_terms: D023061:Gene Order; D005816:Genetic Complementation Test; D056426:Genetic Loci; D006861:Hydrogen Peroxide / Q000494:pharmacology; D051150:Methionine Sulfoxide Reductases / Q000235:genetics*; D050296:Microbial Viability / Q000235:genetics* / Q000276:immunology*; D009504:Neutrophils / Q000382:microbiology* / Q000502:physiology*; D018384:Oxidative Stress; D009195:Peroxidase / Q000378:metabolism; D012486:Salmonella typhimurium / Q000235:genetics* / Q000254:growth & development / Q000276:immunology*; D017384:Sequence Deletion
chemical_list: D006861:Hydrogen Peroxide; D009195:Peroxidase; D051150:Methionine Sulfoxide Reductases
keywords: HOCl; Methionine sulfoxide reductase A; Myeloperoxidase; Neutrophil; Salmonella