Contribution of the Mn-cofactored superoxide dismutase (SodA) to the virulence of Yersinia enterocolitica serotype O8.
Enteric pathogens harbor a set of enzymes (e.g., superoxide dismutases [SOD]) for detoxification of endogenous and exogenous reactive oxygen species which are encountered during infection. To analyze the role of the Mn-cofactored SOD (SodA) in the pathogenicity of yersiniae, we cloned the sodA gene of Yersinia enterocolitica serotype O8 by complementation of an Escherichia coli sodA sodB mutant and subsequently constructed an isogenic mutant by allelic exchange. Sequence analysis revealed an open reading frame that enabled the deduction of a sequence of 207 amino acids with 85% identity to SodA of E. coli. In a mouse infection model, the sodA null mutant was strongly attenuated in comparison to its parental strain. After intravenous infection, the survival and multiplication of the mutant in the spleen and liver were markedly reduced. In contrast, inactivation of sodA had only minor effects on survival and multiplication in the gut and Peyer's patches, as could be demonstrated in the orogastric infection model. The reduction in virulence was accompanied by a low but significant increase of susceptibility of the soda mutant to bacterial killing by polymorphonuclear leukocytes (PMN) and an alteration of the intracellular chemiluminescence response of PMN. These results suggest that the resistance of Y. enterocolitica to exogenous oxygen radicals produced by phagocytes involves the Mn-cofactored SOD. The important role of sodA for the pathogenicity of Y. enterocolitica could also be due to detoxification of endogenous, metabolically produced oxygen radicals which are encountered by extracellular enteric pathogens during the invasion of the host.
Roggenkamp
A
A
Max von Pettenkofer Institute for Hygiene and Microbiology, Ludwig Maximilians University Munich, Germany.
Bittner
T
T
Leitritz
L
L
Sing
A
A
Heesemann
J
J
D000818:Animals; D001483:Base Sequence; D003001:Cloning, Molecular; D005260:Female; D006801:Humans; D008163:Luminescent Measurements; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D009154:Mutation; D009504:Neutrophils / Q000276:immunology; D013482:Superoxide Dismutase / Q000235:genetics / Q000502:physiology*; D014774:Virulence; D015008:Yersinia enterocolitica / Q000472:pathogenicity*
D013482:Superoxide Dismutase