Role of Salmonella typhimurium Mn-superoxide dismutase (SodA) in protection against early killing by J774 macrophages.
The Salmonella typhimurium gene for Mn-cofactored superoxide dismutase (sodA) was cloned by complementation of an Escherichia coli sodA sodB mutant for growth on minimal medium. Sequence analysis revealed an open reading frame of 618 bp encoding a polypeptide with 97% identity to E. coli SodA. A S. typhimurium sodA mutant was created by allelic exchange and tested for the ability to survive in the murine macrophage-like cell line J774. Growth of bacteria under iron-limiting conditions, inactivation of the Fur repressor, or expression of sodA from a plasmid resulted in increased resistance to early killing by J774 cells, which was abolished in the sodA mutant. These results suggest that resistance to the early oxygen-dependent microbicidal mechanisms of phagocytes involves the SodA gene product. The S. typhimurium sodA mutant was not significantly attenuated in mice, however, which suggests that resistance to early oxygen-dependent microbicidal mechanisms in vivo may play only a minor role in Salmonella pathogenesis.
Tsolis
R M
RM
Department of Molecular Microbiology and Immunology, Oregon Health Sciences University, Portland 97201, USA.
Bäumler
A J
AJ
Heffron
F
F
D000595:Amino Acid Sequence; D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics; D001483:Base Sequence; D002460:Cell Line; D003001:Cloning, Molecular; D004926:Escherichia coli / Q000235:genetics; D005798:Genes, Bacterial / Q000235:genetics; D000090463:Iron Deficiencies; D008264:Macrophages / Q000276:immunology* / Q000382:microbiology; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D009154:Mutation; D012097:Repressor Proteins / Q000235:genetics; D012480:Salmonella Infections / Q000209:etiology; D012486:Salmonella typhimurium / Q000201:enzymology* / Q000235:genetics / Q000472:pathogenicity*; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid; D013482:Superoxide Dismutase / Q000235:genetics / Q000502:physiology*; D014774:Virulence / Q000235:genetics
D001426:Bacterial Proteins; D012097:Repressor Proteins; C068477:ferric uptake regulating proteins, bacterial; D013482:Superoxide Dismutase