title: Bacterial copper- and zinc-cofactored superoxide dismutase contributes to the pathogenesis of systemic salmonellosis.
abstract: Copper/zinc-cofactored superoxide dismutase ([Cu,Zn]-SOD) has been found in the periplasm of many bacterial species but its biological function is unknown. Here we report the cloning and characterization of sodC, encoding [Cu,Zn]-SOD, from Salmonella typhimurium. The predicted protein sequence shows only 58% identity to Escherichia coil SodC, and from this its chromosomal location and its immediate proximity to a phage gene, sodC, in Salmonella is speculated to have been acquired by bacteriophage-mediated horizontal transfer from an unknown donor. A sodC mutant of S. typhimurium was unimpaired on aerobic growth in rich medium but showed enhanced sensitivity in vitro to the microbicidal action of superoxide. S. typhimurium, S. choleraesuis and S. dublin sodC mutants showed reduced lethality in a mouse model of oral infection and persisted in significantly lower numbers in livers and spleens after intraperitoneal infection, suggesting that [Cu,Zn]-SOD plays a role in pathogenicity, protecting Salmonella against oxygen radical-mediated host defences. There was, however, no observable difference compared with wild type in the interaction of sodC mutants with porcine pleural, mouse peritoneal or J774 macrophages in vitro, perhaps reflecting the hierarchical capacity of different macrophage lines to kill Salmonella, the most efficient overwhelming the proposed protective effect of periplasmic SOD.
authors.affiliation: Department of Paediatrics, Imperial College School of Medicine at St Mary's, Norfolk Place, London, UK.
authors.forename: J L
authors.initials: JL
authors.lastname: Farrant
authors.forename: A
authors.initials: A
authors.lastname: Sansone
authors.forename: J R
authors.initials: JR
authors.lastname: Canvin
authors.forename: M J
authors.initials: MJ
authors.lastname: Pallen
authors.forename: P R
authors.initials: PR
authors.lastname: Langford
authors.forename: T S
authors.initials: TS
authors.lastname: Wallis
authors.forename: G
authors.initials: G
authors.lastname: Dougan
authors.forename: J S
authors.initials: JS
authors.lastname: Kroll
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002455:Cell Division; D002874:Chromosome Mapping; D003001:Cloning, Molecular; D005260:Female; D007413:Intestinal Mucosa / Q000382:microbiology; D008264:Macrophages / Q000382:microbiology; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D009059:Mouth Diseases / Q000382:microbiology; D011994:Recombinant Proteins / Q000096:biosynthesis; D012481:Salmonella Infections, Animal / Q000382:microbiology*; D012486:Salmonella typhimurium / Q000201:enzymology* / Q000235:genetics / Q000472:pathogenicity; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism*; D014774:Virulence
chemical_list: D011994:Recombinant Proteins; D013482:Superoxide Dismutase