Skip to main content
PMC home page
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1996 Jul 23;93(15):7800–7804. doi: 10.1073/pnas.93.15.7800

Identification of a pathogenicity island required for Salmonella survival in host cells.

H Ochman 1, F C Soncini 1, F Solomon 1, E A Groisman 1
PMCID: PMC38828  PMID: 8755556

Abstract

We have identified a region unique to the Salmonella typhimurium chromosome that is essential for virulence in mice. This region harbors at least three genes: two (spiA and spiB) encode products that are similar to proteins found in type III secretion systems, and a third (spiR) encodes a putative regulator. A strain with a mutation in spiA was unable to survive within macrophages but displayed wild-type levels of epithelial cell invasion. The culture supernatants of the spi mutants lacked a modified form of flagellin, which was present in the supernatant of the wild-type strain. This suggests that the Spi secretory apparatus exports a protease, or a protein that can alter the activity of a secreted protease. The "pathogenicity island" harboring the spi genes may encode the virulence determinants that set Salmonella apart from other enteric pathogens.

Full text

PDF
7802

Images in this article

7802Fig. 2
on p.7802
7803Fig. 4
on p.7803

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Alpuche Aranda C. M., Swanson J. A., Loomis W. P., Miller S. I. Salmonella typhimurium activates virulence gene transcription within acidified macrophage phagosomes. Proc Natl Acad Sci U S A. 1992 Nov 1;89(21):10079–10083. doi: 10.1073/pnas.89.21.10079. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Blum G., Ott M., Lischewski A., Ritter A., Imrich H., Tschäpe H., Hacker J. Excision of large DNA regions termed pathogenicity islands from tRNA-specific loci in the chromosome of an Escherichia coli wild-type pathogen. Infect Immun. 1994 Feb;62(2):606–614. doi: 10.1128/iai.62.2.606-614.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Buchmeier N. A., Heffron F. Intracellular survival of wild-type Salmonella typhimurium and macrophage-sensitive mutants in diverse populations of macrophages. Infect Immun. 1989 Jan;57(1):1–7. doi: 10.1128/iai.57.1.1-7.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Bäumler A. J., Kusters J. G., Stojiljkovic I., Heffron F. Salmonella typhimurium loci involved in survival within macrophages. Infect Immun. 1994 May;62(5):1623–1630. doi: 10.1128/iai.62.5.1623-1630.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Chang C., Meyerowitz E. M. Eukaryotes have "two-component" signal transducers. Res Microbiol. 1994 Jun-Aug;145(5-6):481–486. doi: 10.1016/0923-2508(94)90097-3. [DOI] [PubMed] [Google Scholar]
  6. 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]
  7. Fetherston J. D., Schuetze P., Perry R. D. Loss of the pigmentation phenotype in Yersinia pestis is due to the spontaneous deletion of 102 kb of chromosomal DNA which is flanked by a repetitive element. Mol Microbiol. 1992 Sep;6(18):2693–2704. doi: 10.1111/j.1365-2958.1992.tb01446.x. [DOI] [PubMed] [Google Scholar]
  8. Fields P. I., Swanson R. V., Haidaris C. G., Heffron F. Mutants of Salmonella typhimurium that cannot survive within the macrophage are avirulent. Proc Natl Acad Sci U S A. 1986 Jul;83(14):5189–5193. doi: 10.1073/pnas.83.14.5189. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Finlay B. B. Molecular and cellular mechanisms of Salmonella pathogenesis. Curr Top Microbiol Immunol. 1994;192:163–185. doi: 10.1007/978-3-642-78624-2_8. [DOI] [PubMed] [Google Scholar]
  10. Galán J. E., Curtiss R., 3rd Cloning and molecular characterization of genes whose products allow Salmonella typhimurium to penetrate tissue culture cells. Proc Natl Acad Sci U S A. 1989 Aug;86(16):6383–6387. doi: 10.1073/pnas.86.16.6383. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Garcia-del Portillo F., Finlay B. B. Targeting of Salmonella typhimurium to vesicles containing lysosomal membrane glycoproteins bypasses compartments with mannose 6-phosphate receptors. J Cell Biol. 1995 Apr;129(1):81–97. doi: 10.1083/jcb.129.1.81. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Groisman E. A., Ochman H. Cognate gene clusters govern invasion of host epithelial cells by Salmonella typhimurium and Shigella flexneri. EMBO J. 1993 Oct;12(10):3779–3787. doi: 10.1002/j.1460-2075.1993.tb06056.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Groisman E. A., Ochman H. How to become a pathogen. Trends Microbiol. 1994 Aug;2(8):289–294. doi: 10.1016/0966-842x(94)90006-x. [DOI] [PubMed] [Google Scholar]
  14. Groisman E. A., Sturmoski M. A., Solomon F. R., Lin R., Ochman H. Molecular, functional, and evolutionary analysis of sequences specific to Salmonella. Proc Natl Acad Sci U S A. 1993 Feb 1;90(3):1033–1037. doi: 10.1073/pnas.90.3.1033. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Hensel M., Shea J. E., Gleeson C., Jones M. D., Dalton E., Holden D. W. Simultaneous identification of bacterial virulence genes by negative selection. Science. 1995 Jul 21;269(5222):400–403. doi: 10.1126/science.7618105. [DOI] [PubMed] [Google Scholar]
  16. Inouye S., Sunshine M. G., Six E. W., Inouye M. Retronphage phi R73: an E. coli phage that contains a retroelement and integrates into a tRNA gene. Science. 1991 May 17;252(5008):969–971. doi: 10.1126/science.1709758. [DOI] [PubMed] [Google Scholar]
  17. Jarvis K. G., Girón J. A., Jerse A. E., McDaniel T. K., Donnenberg M. S., Kaper J. B. Enteropathogenic Escherichia coli contains a putative type III secretion system necessary for the export of proteins involved in attaching and effacing lesion formation. Proc Natl Acad Sci U S A. 1995 Aug 15;92(17):7996–8000. doi: 10.1073/pnas.92.17.7996. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Kaniga K., Bossio J. C., Galán J. E. The Salmonella typhimurium invasion genes invF and invG encode homologues of the AraC and PulD family of proteins. Mol Microbiol. 1994 Aug;13(4):555–568. doi: 10.1111/j.1365-2958.1994.tb00450.x. [DOI] [PubMed] [Google Scholar]
  19. Lee C. A., Jones B. D., Falkow S. Identification of a Salmonella typhimurium invasion locus by selection for hyperinvasive mutants. Proc Natl Acad Sci U S A. 1992 Mar 1;89(5):1847–1851. doi: 10.1073/pnas.89.5.1847. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Li J., Ochman H., Groisman E. A., Boyd E. F., Solomon F., Nelson K., Selander R. K. Relationship between evolutionary rate and cellular location among the Inv/Spa invasion proteins of Salmonella enterica. Proc Natl Acad Sci U S A. 1995 Aug 1;92(16):7252–7256. doi: 10.1073/pnas.92.16.7252. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Libby S. J., Goebel W., Ludwig A., Buchmeier N., Bowe F., Fang F. C., Guiney D. G., Songer J. G., Heffron F. A cytolysin encoded by Salmonella is required for survival within macrophages. Proc Natl Acad Sci U S A. 1994 Jan 18;91(2):489–493. doi: 10.1073/pnas.91.2.489. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. McDaniel T. K., Jarvis K. G., Donnenberg M. S., Kaper J. B. A genetic locus of enterocyte effacement conserved among diverse enterobacterial pathogens. Proc Natl Acad Sci U S A. 1995 Feb 28;92(5):1664–1668. doi: 10.1073/pnas.92.5.1664. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Michiels T., Vanooteghem J. C., Lambert de Rouvroit C., China B., Gustin A., Boudry P., Cornelis G. R. Analysis of virC, an operon involved in the secretion of Yop proteins by Yersinia enterocolitica. J Bacteriol. 1991 Aug;173(16):4994–5009. doi: 10.1128/jb.173.16.4994-5009.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Mills D. M., Bajaj V., Lee C. A. A 40 kb chromosomal fragment encoding Salmonella typhimurium invasion genes is absent from the corresponding region of the Escherichia coli K-12 chromosome. Mol Microbiol. 1995 Feb;15(4):749–759. doi: 10.1111/j.1365-2958.1995.tb02382.x. [DOI] [PubMed] [Google Scholar]
  25. Nagasawa S., Tokishita S., Aiba H., Mizuno T. A novel sensor-regulator protein that belongs to the homologous family of signal-transduction proteins involved in adaptive responses in Escherichia coli. Mol Microbiol. 1992 Mar;6(6):799–807. doi: 10.1111/j.1365-2958.1992.tb01530.x. [DOI] [PubMed] [Google Scholar]
  26. Ochman H., Groisman E. A. The evolution of invasion by enteric bacteria. Can J Microbiol. 1995 Jul;41(7):555–561. doi: 10.1139/m95-074. [DOI] [PubMed] [Google Scholar]
  27. Ochman H., Groisman E. A. The origin and evolution of species differences in Escherichia coli and Salmonella typhimurium. EXS. 1994;69:479–493. doi: 10.1007/978-3-0348-7527-1_27. [DOI] [PubMed] [Google Scholar]
  28. Parsot C. Shigella flexneri: genetics of entry and intercellular dissemination in epithelial cells. Curr Top Microbiol Immunol. 1994;192:217–241. doi: 10.1007/978-3-642-78624-2_10. [DOI] [PubMed] [Google Scholar]
  29. Roth J. R., Lawrence J. G., Rubenfield M., Kieffer-Higgins S., Church G. M. Characterization of the cobalamin (vitamin B12) biosynthetic genes of Salmonella typhimurium. J Bacteriol. 1993 Jun;175(11):3303–3316. doi: 10.1128/jb.175.11.3303-3316.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Salmond G. P., Reeves P. J. Membrane traffic wardens and protein secretion in gram-negative bacteria. Trends Biochem Sci. 1993 Jan;18(1):7–12. doi: 10.1016/0968-0004(93)90080-7. [DOI] [PubMed] [Google Scholar]
  31. Sanderson K. E., Hessel A., Rudd K. E. Genetic map of Salmonella typhimurium, edition VIII. Microbiol Rev. 1995 Jun;59(2):241–303. doi: 10.1128/mr.59.2.241-303.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Van Gijsegem F., Gough C., Zischek C., Niqueux E., Arlat M., Genin S., Barberis P., German S., Castello P., Boucher C. The hrp gene locus of Pseudomonas solanacearum, which controls the production of a type III secretion system, encodes eight proteins related to components of the bacterial flagellar biogenesis complex. Mol Microbiol. 1995 Mar;15(6):1095–1114. doi: 10.1111/j.1365-2958.1995.tb02284.x. [DOI] [PubMed] [Google Scholar]
  33. Wei Z. M., Beer S. V. HrpI of Erwinia amylovora functions in secretion of harpin and is a member of a new protein family. J Bacteriol. 1993 Dec;175(24):7958–7967. doi: 10.1128/jb.175.24.7958-7967.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES