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. 1997 Aug;65(8):3412–3421. doi: 10.1128/iai.65.8.3412-3421.1997

Invasin-dependent and invasin-independent pathways for translocation of Yersinia pseudotuberculosis across the Peyer's patch intestinal epithelium.

A Marra 1, R R Isberg 1
PMCID: PMC175483  PMID: 9234806

Abstract

Yersinia pseudotuberculosis initiates systemic disease after translocation across the intestinal epithelium. Three Y. pseudotuberculosis factors, previously identified by their ability to promote association with cultured cells, were evaluated for their relative roles in translocation. To this end, mutants defective for invasin, YadA, or pH 6 antigen were tested for movement from the intestinal lumen into the subepithelium. Within 45 min after introduction of bacteria into the lumen, wild-type bacteria were found in the Peyer's patch. Mutants expressing defective invasin derivatives were unable to promote efficient translocation into the Peyer's patch and instead colonized on the luminal surface of the intestinal epithelium. In particular, a translocation defect was observed in a Y. pseudotuberculosis strain that expressed an uptake-defective invasin protein retaining considerable receptor binding activity. To attempt to reduce binding to luminal mucus, Y. pseudotuberculosis yadA and inv yadA strains were analyzed. Both strains had reduced mucus binding, with the inv yadA mutant revealing an alternate uptake pathway that was invasin independent. A mutant defective in the production of the pH 6 antigen adhesin also showed reduced binding to luminal mucus, with specific localization of bacteria in M cells. These results indicate that Y. pseudotuberculosis adhesive factors control the site of bacterial interaction within the intestinal environment and that loss of one factor causes drastic changes in the preferred site of localization of the bacterium in this locale.

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Selected References

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  1. Biot T., Cornelis G. R. The replication, partition and yop regulation of the pYV plasmids are highly conserved in Yersinia enterocolitica and Y. pseudotuberculosis. J Gen Microbiol. 1988 Jun;134(6):1525–1534. doi: 10.1099/00221287-134-6-1525. [DOI] [PubMed] [Google Scholar]
  2. Bliska J. B., Copass M. C., Falkow S. The Yersinia pseudotuberculosis adhesin YadA mediates intimate bacterial attachment to and entry into HEp-2 cells. Infect Immun. 1993 Sep;61(9):3914–3921. doi: 10.1128/iai.61.9.3914-3921.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bovallius A., Nilsson G. Ingestion and survival of Y. pseudotuberculosis in HeLa cells. Can J Microbiol. 1975 Dec;21(12):1997–2007. doi: 10.1139/m75-287. [DOI] [PubMed] [Google Scholar]
  4. Brubaker R. R. The genus Yersinia: biochemistry and genetics of virulence. Curr Top Microbiol Immunol. 1972;57:111–158. doi: 10.1007/978-3-642-65297-4_4. [DOI] [PubMed] [Google Scholar]
  5. Bye W. A., Allan C. H., Trier J. S. Structure, distribution, and origin of M cells in Peyer's patches of mouse ileum. Gastroenterology. 1984 May;86(5 Pt 1):789–801. [PubMed] [Google Scholar]
  6. Clark M. A., Jepson M. A., Simmons N. L., Booth T. A., Hirst B. H. Differential expression of lectin-binding sites defines mouse intestinal M-cells. J Histochem Cytochem. 1993 Nov;41(11):1679–1687. doi: 10.1177/41.11.7691933. [DOI] [PubMed] [Google Scholar]
  7. Cornelis G. R., Biot T., Lambert de Rouvroit C., Michiels T., Mulder B., Sluiters C., Sory M. P., Van Bouchaute M., Vanooteghem J. C. The Yersinia yop regulon. Mol Microbiol. 1989 Oct;3(10):1455–1459. doi: 10.1111/j.1365-2958.1989.tb00129.x. [DOI] [PubMed] [Google Scholar]
  8. De Strooper B., Van Leuven F., Carmeliet G., Van Den Berghe H., Cassiman J. J. Cultured human fibroblasts contain a large pool of precursor beta 1-integrin but lack an intracellular pool of mature subunit. Eur J Biochem. 1991 Jul 1;199(1):25–33. doi: 10.1111/j.1432-1033.1991.tb16087.x. [DOI] [PubMed] [Google Scholar]
  9. De Strooper B., Van der Schueren B., Jaspers M., Saison M., Spaepen M., Van Leuven F., Van den Berghe H., Cassiman J. J. Distribution of the beta 1 subgroup of the integrins in human cells and tissues. J Histochem Cytochem. 1989 Mar;37(3):299–307. doi: 10.1177/37.3.2645360. [DOI] [PubMed] [Google Scholar]
  10. Emödy L., Heesemann J., Wolf-Watz H., Skurnik M., Kapperud G., O'Toole P., Wadström T. Binding to collagen by Yersinia enterocolitica and Yersinia pseudotuberculosis: evidence for yopA-mediated and chromosomally encoded mechanisms. J Bacteriol. 1989 Dec;171(12):6674–6679. doi: 10.1128/jb.171.12.6674-6679.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Falk P., Roth K. A., Gordon J. I. Lectins are sensitive tools for defining the differentiation programs of mouse gut epithelial cell lineages. Am J Physiol. 1994 Jun;266(6 Pt 1):G987–1003. doi: 10.1152/ajpgi.1994.266.6.G987. [DOI] [PubMed] [Google Scholar]
  12. Gemski P., Lazere J. R., Casey T., Wohlhieter J. A. Presence of a virulence-associated plasmid in Yersinia pseudotuberculosis. Infect Immun. 1980 Jun;28(3):1044–1047. doi: 10.1128/iai.28.3.1044-1047.1980. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Giannasca P. J., Giannasca K. T., Falk P., Gordon J. I., Neutra M. R. Regional differences in glycoconjugates of intestinal M cells in mice: potential targets for mucosal vaccines. Am J Physiol. 1994 Dec;267(6 Pt 1):G1108–G1121. doi: 10.1152/ajpgi.1994.267.6.G1108. [DOI] [PubMed] [Google Scholar]
  14. Hynes R. O. Integrins: a family of cell surface receptors. Cell. 1987 Feb 27;48(4):549–554. doi: 10.1016/0092-8674(87)90233-9. [DOI] [PubMed] [Google Scholar]
  15. Isberg R. R. Determinants for thermoinducible cell binding and plasmid-encoded cellular penetration detected in the absence of the Yersinia pseudotuberculosis invasin protein. Infect Immun. 1989 Jul;57(7):1998–2005. doi: 10.1128/iai.57.7.1998-2005.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Isberg R. R., Leong J. M. Multiple beta 1 chain integrins are receptors for invasin, a protein that promotes bacterial penetration into mammalian cells. Cell. 1990 Mar 9;60(5):861–871. doi: 10.1016/0092-8674(90)90099-z. [DOI] [PubMed] [Google Scholar]
  17. Isberg R. R., Voorhis D. L., Falkow S. Identification of invasin: a protein that allows enteric bacteria to penetrate cultured mammalian cells. Cell. 1987 Aug 28;50(5):769–778. doi: 10.1016/0092-8674(87)90335-7. [DOI] [PubMed] [Google Scholar]
  18. Leong J. M., Fournier R. S., Isberg R. R. Identification of the integrin binding domain of the Yersinia pseudotuberculosis invasin protein. EMBO J. 1990 Jun;9(6):1979–1989. doi: 10.1002/j.1460-2075.1990.tb08326.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Leong J. M., Fournier R. S., Isberg R. R. Mapping and topographic localization of epitopes of the Yersinia pseudotuberculosis invasin protein. Infect Immun. 1991 Oct;59(10):3424–3433. doi: 10.1128/iai.59.10.3424-3433.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Leong J. M., Moitoso de Vargas L., Isberg R. R. Binding of cultured mammalian cells to immobilized bacteria. Infect Immun. 1992 Feb;60(2):683–686. doi: 10.1128/iai.60.2.683-686.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Leong J. M., Morrissey P. E., Marra A., Isberg R. R. An aspartate residue of the Yersinia pseudotuberculosis invasin protein that is critical for integrin binding. EMBO J. 1995 Feb 1;14(3):422–431. doi: 10.1002/j.1460-2075.1995.tb07018.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Lian C. J., Hwang W. S., Kelly J. K., Pai C. H. Invasiveness of Yersinia enterocolitica lacking the virulence plasmid: an in-vivo study. J Med Microbiol. 1987 Nov;24(3):219–226. doi: 10.1099/00222615-24-3-219. [DOI] [PubMed] [Google Scholar]
  23. Miller V. L., Falkow S. Evidence for two genetic loci in Yersinia enterocolitica that can promote invasion of epithelial cells. Infect Immun. 1988 May;56(5):1242–1248. doi: 10.1128/iai.56.5.1242-1248.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Neutra M. R., Kraehenbuhl J. P. Transepithelial transport and mucosal defence I: the role of M cells. Trends Cell Biol. 1992 May;2(5):134–138. doi: 10.1016/0962-8924(92)90099-9. [DOI] [PubMed] [Google Scholar]
  25. Paerregaard A., Espersen F., Skurnik M. Adhesion of yersiniae to rabbit intestinal constituents: role of outer membrane protein YadA and modulation by intestinal mucus. Contrib Microbiol Immunol. 1991;12:171–175. [PubMed] [Google Scholar]
  26. Pepe J. C., Miller V. L. Yersinia enterocolitica invasin: a primary role in the initiation of infection. Proc Natl Acad Sci U S A. 1993 Jul 15;90(14):6473–6477. doi: 10.1073/pnas.90.14.6473. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Pepe J. C., Wachtel M. R., Wagar E., Miller V. L. Pathogenesis of defined invasion mutants of Yersinia enterocolitica in a BALB/c mouse model of infection. Infect Immun. 1995 Dec;63(12):4837–4848. doi: 10.1128/iai.63.12.4837-4848.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Portnoy D. A., Wolf-Watz H., Bolin I., Beeder A. B., Falkow S. Characterization of common virulence plasmids in Yersinia species and their role in the expression of outer membrane proteins. Infect Immun. 1984 Jan;43(1):108–114. doi: 10.1128/iai.43.1.108-114.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Richardson M., Harkness T. K. Intracellular Pasteurella pseudotuberculosis: Multiplication in Cultured Spleen and Kidney Cells. Infect Immun. 1970 Nov;2(5):631–639. doi: 10.1128/iai.2.5.631-639.1970. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Rosqvist R., Skurnik M., Wolf-Watz H. Increased virulence of Yersinia pseudotuberculosis by two independent mutations. Nature. 1988 Aug 11;334(6182):522–524. doi: 10.1038/334522a0. [DOI] [PubMed] [Google Scholar]
  31. 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]
  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. Tertti R., Skurnik M., Vartio T., Kuusela P. Adhesion protein YadA of Yersinia species mediates binding of bacteria to fibronectin. Infect Immun. 1992 Jul;60(7):3021–3024. doi: 10.1128/iai.60.7.3021-3024.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Tran Van Nhieu G., Isberg R. R. Bacterial internalization mediated by beta 1 chain integrins is determined by ligand affinity and receptor density. EMBO J. 1993 May;12(5):1887–1895. doi: 10.1002/j.1460-2075.1993.tb05837.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Une T. Studies on the pathogenicity of Yersinia enterocolitica. III. Comparative studies between Y. enterocolitica and Y. pseudotuberculosis. Microbiol Immunol. 1977;21(9):505–516. doi: 10.1111/j.1348-0421.1977.tb00316.x. [DOI] [PubMed] [Google Scholar]
  36. Yang Y., Isberg R. R. Cellular internalization in the absence of invasin expression is promoted by the Yersinia pseudotuberculosis yadA product. Infect Immun. 1993 Sep;61(9):3907–3913. doi: 10.1128/iai.61.9.3907-3913.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Yang Y., Merriam J. J., Mueller J. P., Isberg R. R. The psa locus is responsible for thermoinducible binding of Yersinia pseudotuberculosis to cultured cells. Infect Immun. 1996 Jul;64(7):2483–2489. doi: 10.1128/iai.64.7.2483-2489.1996. [DOI] [PMC free article] [PubMed] [Google Scholar]

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