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. 1997 Nov;65(11):4705–4710. doi: 10.1128/iai.65.11.4705-4710.1997

Contribution of the Mn-cofactored superoxide dismutase (SodA) to the virulence of Yersinia enterocolitica serotype O8.

A Roggenkamp 1, T Bittner 1, L Leitritz 1, A Sing 1, J Heesemann 1
PMCID: PMC175675  PMID: 9353054

Abstract

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.

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Selected References

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  1. Autenrieth I. B., Firsching R. Penetration of M cells and destruction of Peyer's patches by Yersinia enterocolitica: an ultrastructural and histological study. J Med Microbiol. 1996 Apr;44(4):285–294. doi: 10.1099/00222615-44-4-285. [DOI] [PubMed] [Google Scholar]
  2. Beauchamp C., Fridovich I. Superoxide dismutase: improved assays and an assay applicable to acrylamide gels. Anal Biochem. 1971 Nov;44(1):276–287. doi: 10.1016/0003-2697(71)90370-8. [DOI] [PubMed] [Google Scholar]
  3. Bliska J. B., Guan K. L., Dixon J. E., Falkow S. Tyrosine phosphate hydrolysis of host proteins by an essential Yersinia virulence determinant. Proc Natl Acad Sci U S A. 1991 Feb 15;88(4):1187–1191. doi: 10.1073/pnas.88.4.1187. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Briheim G., Stendahl O., Dahlgren C. Intra- and extracellular events in luminol-dependent chemiluminescence of polymorphonuclear leukocytes. Infect Immun. 1984 Jul;45(1):1–5. doi: 10.1128/iai.45.1.1-5.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Cornelis G. R. Yersinia pathogenicity factors. Curr Top Microbiol Immunol. 1994;192:243–263. doi: 10.1007/978-3-642-78624-2_11. [DOI] [PubMed] [Google Scholar]
  6. Cover T. L., Aber R. C. Yersinia enterocolitica. N Engl J Med. 1989 Jul 6;321(1):16–24. doi: 10.1056/NEJM198907063210104. [DOI] [PubMed] [Google Scholar]
  7. Dahlgren C. Polymorphonuclear leukocyte chemiluminescence induced by formylmethionyl-leucyl-phenylalanine and phorbol myristate acetate: effects of catalase and superoxide dismutase. Agents Actions. 1987 Jun;21(1-2):104–112. doi: 10.1007/BF01974930. [DOI] [PubMed] [Google Scholar]
  8. DeChatelet L. R., Long G. D., Shirley P. S., Bass D. A., Thomas M. J., Henderson F. W., Cohen M. S. Mechanism of the luminol-dependent chemiluminescence of human neutrophils. J Immunol. 1982 Oct;129(4):1589–1593. [PubMed] [Google Scholar]
  9. Ewald J. H., Heesemann J., Rüdiger H., Autenrieth I. B. Interaction of polymorphonuclear leukocytes with Yersinia enterocolitica: role of the Yersinia virulence plasmid and modulation by the iron-chelator desferrioxamine B. J Infect Dis. 1994 Jul;170(1):140–150. doi: 10.1093/infdis/170.1.140. [DOI] [PubMed] [Google Scholar]
  10. Fee J. A. Regulation of sod genes in Escherichia coli: relevance to superoxide dismutase function. Mol Microbiol. 1991 Nov;5(11):2599–2610. doi: 10.1111/j.1365-2958.1991.tb01968.x. [DOI] [PubMed] [Google Scholar]
  11. Franzon V. L., Arondel J., Sansonetti P. J. Contribution of superoxide dismutase and catalase activities to Shigella flexneri pathogenesis. Infect Immun. 1990 Feb;58(2):529–535. doi: 10.1128/iai.58.2.529-535.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Guiney D. G., Helinski D. R. The DNA-protein relaxation complex of the plasmid RK2: location of the site-specific nick in the region of the proposed origin of transfer. Mol Gen Genet. 1979 Oct 3;176(2):183–189. doi: 10.1007/BF00273212. [DOI] [PubMed] [Google Scholar]
  13. Hanahan D. Studies on transformation of Escherichia coli with plasmids. J Mol Biol. 1983 Jun 5;166(4):557–580. doi: 10.1016/s0022-2836(83)80284-8. [DOI] [PubMed] [Google Scholar]
  14. Hanski C., Kutschka U., Schmoranzer H. P., Naumann M., Stallmach A., Hahn H., Menge H., Riecken E. O. Immunohistochemical and electron microscopic study of interaction of Yersinia enterocolitica serotype O8 with intestinal mucosa during experimental enteritis. Infect Immun. 1989 Mar;57(3):673–678. doi: 10.1128/iai.57.3.673-678.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Heesemann J., Keller C., Morawa R., Schmidt N., Siemens H. J., Laufs R. Plasmids of human strains of Yersinia enterocolitica: molecular relatedness and possible importance for pathogenesis. J Infect Dis. 1983 Jan;147(1):107–115. doi: 10.1093/infdis/147.1.107. [DOI] [PubMed] [Google Scholar]
  16. Heesemann J., Laufs R. Construction of a mobilizable Yersinia enterocolitica virulence plasmid. J Bacteriol. 1983 Aug;155(2):761–767. doi: 10.1128/jb.155.2.761-767.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Lian C. J., Hwang W. S., Pai C. H. Plasmid-mediated resistance to phagocytosis in Yersinia enterocolitica. Infect Immun. 1987 May;55(5):1176–1183. doi: 10.1128/iai.55.5.1176-1183.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Miller R. A., Britigan B. E. Role of oxidants in microbial pathophysiology. Clin Microbiol Rev. 1997 Jan;10(1):1–18. doi: 10.1128/cmr.10.1.1. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Miller V. L., Mekalanos J. J. A novel suicide vector and its use in construction of insertion mutations: osmoregulation of outer membrane proteins and virulence determinants in Vibrio cholerae requires toxR. J Bacteriol. 1988 Jun;170(6):2575–2583. doi: 10.1128/jb.170.6.2575-2583.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Persson C., Nordfelth R., Holmström A., Håkansson S., Rosqvist R., Wolf-Watz H. Cell-surface-bound Yersinia translocate the protein tyrosine phosphatase YopH by a polarized mechanism into the target cell. Mol Microbiol. 1995 Oct;18(1):135–150. doi: 10.1111/j.1365-2958.1995.mmi_18010135.x. [DOI] [PubMed] [Google Scholar]
  21. Rakin A., Saken E., Harmsen D., Heesemann J. The pesticin receptor of Yersinia enterocolitica: a novel virulence factor with dual function. Mol Microbiol. 1994 Jul;13(2):253–263. doi: 10.1111/j.1365-2958.1994.tb00420.x. [DOI] [PubMed] [Google Scholar]
  22. Roggenkamp A., Neuberger H. R., Flügel A., Schmoll T., Heesemann J. Substitution of two histidine residues in YadA protein of Yersinia enterocolitica abrogates collagen binding, cell adherence and mouse virulence. Mol Microbiol. 1995 Jun;16(6):1207–1219. doi: 10.1111/j.1365-2958.1995.tb02343.x. [DOI] [PubMed] [Google Scholar]
  23. Roggenkamp A., Schubert S., Jacobi C. A., Heesemann J. Dissection of the Yersinia enterocolitica virulence plasmid pYVO8 into an operating unit and virulence gene modules. FEMS Microbiol Lett. 1995 Dec 1;134(1):69–73. doi: 10.1111/j.1574-6968.1995.tb07916.x. [DOI] [PubMed] [Google Scholar]
  24. Rosqvist R., Bölin I., Wolf-Watz H. Inhibition of phagocytosis in Yersinia pseudotuberculosis: a virulence plasmid-encoded ability involving the Yop2b protein. Infect Immun. 1988 Aug;56(8):2139–2143. doi: 10.1128/iai.56.8.2139-2143.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Rosqvist R., Forsberg A., Rimpiläinen M., Bergman T., Wolf-Watz H. The cytotoxic protein YopE of Yersinia obstructs the primary host defence. Mol Microbiol. 1990 Apr;4(4):657–667. doi: 10.1111/j.1365-2958.1990.tb00635.x. [DOI] [PubMed] [Google Scholar]
  26. Rosqvist R., Magnusson K. E., Wolf-Watz H. Target cell contact triggers expression and polarized transfer of Yersinia YopE cytotoxin into mammalian cells. EMBO J. 1994 Feb 15;13(4):964–972. doi: 10.1002/j.1460-2075.1994.tb06341.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Ruckdeschel K., Roggenkamp A., Schubert S., Heesemann J. Differential contribution of Yersinia enterocolitica virulence factors to evasion of microbicidal action of neutrophils. Infect Immun. 1996 Mar;64(3):724–733. doi: 10.1128/iai.64.3.724-733.1996. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Simonet M., Richard S., Berche P. Electron microscopic evidence for in vivo extracellular localization of Yersinia pseudotuberculosis harboring the pYV plasmid. Infect Immun. 1990 Mar;58(3):841–845. doi: 10.1128/iai.58.3.841-845.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Skrzypek E., Straley S. C. Differential effects of deletions in lcrV on secretion of V antigen, regulation of the low-Ca2+ response, and virulence of Yersinia pestis. J Bacteriol. 1995 May;177(9):2530–2542. doi: 10.1128/jb.177.9.2530-2542.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Skurnik M., Wolf-Watz H. Analysis of the yopA gene encoding the Yop1 virulence determinants of Yersinia spp. Mol Microbiol. 1989 Apr;3(4):517–529. doi: 10.1111/j.1365-2958.1989.tb00198.x. [DOI] [PubMed] [Google Scholar]
  31. Sory M. P., Cornelis G. R. Translocation of a hybrid YopE-adenylate cyclase from Yersinia enterocolitica into HeLa cells. Mol Microbiol. 1994 Nov;14(3):583–594. doi: 10.1111/j.1365-2958.1994.tb02191.x. [DOI] [PubMed] [Google Scholar]
  32. Straley S. C., Skrzypek E., Plano G. V., Bliska J. B. Yops of Yersinia spp. pathogenic for humans. Infect Immun. 1993 Aug;61(8):3105–3110. doi: 10.1128/iai.61.8.3105-3110.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Touati D., Jacques M., Tardat B., Bouchard L., Despied S. Lethal oxidative damage and mutagenesis are generated by iron in delta fur mutants of Escherichia coli: protective role of superoxide dismutase. J Bacteriol. 1995 May;177(9):2305–2314. doi: 10.1128/jb.177.9.2305-2314.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Tsolis R. M., Bäumler A. J., Heffron F. Role of Salmonella typhimurium Mn-superoxide dismutase (SodA) in protection against early killing by J774 macrophages. Infect Immun. 1995 May;63(5):1739–1744. doi: 10.1128/iai.63.5.1739-1744.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Vogel U., Autenrieth I. B., Berner R., Heesemann J. Role of plasmid-encoded antigens of Yersinia enterocolitica in humoral immunity against secondary Y. enterocolitica infection in mice. Microb Pathog. 1993 Jul;15(1):23–36. doi: 10.1006/mpat.1993.1054. [DOI] [PubMed] [Google Scholar]

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