• We are sorry, but NCBI web applications do not support your browser and may not function properly. More information
Logo of pnasPNASInfo for AuthorsSubscriptionsAboutThis Article
Proc Natl Acad Sci U S A. Mar 19, 1996; 93(6): 2593–2597.
PMCID: PMC39842

Identification of a virulence locus encoding a second type III secretion system in Salmonella typhimurium.

Abstract

Mapping the insertion points of 16 signature-tagged transposon mutants on the Salmonella typhimurium chromosome led to the identification of a 40-kb virulence gene cluster at minute 30.7. This locus is conserved among all other Salmonella species examined but is not present in a variety of other pathogenic bacteria or in Escherichia coli K-12. Nucleotide sequencing of a portion of this locus revealed 11 open reading frames whose predicted proteins encode components of a type III secretion system. To distinguish between this and the type III secretion system encoded by the inv/spa invasion locus known to reside on a pathogenicity island, we refer to the inv/spa locus as Salmonella pathogenicity island (SPI) 1 and the new locus as SPI2. SPI2 has a lower G+C content than that of the remainder of the Salmonella genome and is flanked by genes whose products share greater than 90% identity with those of the E. coli ydhE and pykF genes. Thus SPI2 was probably acquired horizontally by insertion into a region corresponding to that between the ydhE and pykF genes of E. coli. Virulence studies of SPI2 mutants have shown them to be attenuated by at least five orders of magnitude compared with the wild-type strain after oral or intraperitoneal inoculation of mice.

Full text

Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (1.3M), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References.

Images in this article

Click on the image to see a larger version.

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Carter PB, Collins FM. The route of enteric infection in normal mice. J Exp Med. 1974 May 1;139(5):1189–1203. [PMC free article] [PubMed]
  • Takeuchi A. Electron microscope studies of experimental Salmonella infection. I. Penetration into the intestinal epithelium by Salmonella typhimurium. Am J Pathol. 1967 Jan;50(1):109–136. [PMC free article] [PubMed]
  • Finlay BB. Molecular and cellular mechanisms of Salmonella pathogenesis. Curr Top Microbiol Immunol. 1994;192:163–185. [PubMed]
  • Groisman EA, Ochman H. How to become a pathogen. Trends Microbiol. 1994 Aug;2(8):289–294. [PubMed]
  • Hensel M, Shea JE, Gleeson C, Jones MD, Dalton E, Holden DW. Simultaneous identification of bacterial virulence genes by negative selection. Science. 1995 Jul 21;269(5222):400–403. [PubMed]
  • Salmond GP, Reeves PJ. Membrane traffic wardens and protein secretion in gram-negative bacteria. Trends Biochem Sci. 1993 Jan;18(1):7–12. [PubMed]
  • Van Gijsegem F, Genin S, Boucher C. Conservation of secretion pathways for pathogenicity determinants of plant and animal bacteria. Trends Microbiol. 1993 Aug;1(5):175–180. [PubMed]
  • Galán JE, 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. [PMC free article] [PubMed]
  • Groisman EA, 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. [PMC free article] [PubMed]
  • Ginocchio CC, Olmsted SB, Wells CL, Galán JE. Contact with epithelial cells induces the formation of surface appendages on Salmonella typhimurium. Cell. 1994 Feb 25;76(4):717–724. [PubMed]
  • Sanderson KE, Hessel A, Rudd KE. Genetic map of Salmonella typhimurium, edition VIII. Microbiol Rev. 1995 Jun;59(2):241–303. [PMC free article] [PubMed]
  • Mills DM, Bajaj V, Lee CA. 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. [PubMed]
  • de Lorenzo V, Timmis KN. Analysis and construction of stable phenotypes in gram-negative bacteria with Tn5- and Tn10-derived minitransposons. Methods Enzymol. 1994;235:386–405. [PubMed]
  • Maurer R, Osmond BC, Shekhtman E, Wong A, Botstein D. Functional interchangeability of DNA replication genes in Salmonella typhimurium and Escherichia coli demonstrated by a general complementation procedure. Genetics. 1984 Sep;108(1):1–23. [PMC free article] [PubMed]
  • Youderian P, Sugiono P, Brewer KL, Higgins NP, Elliott T. Packaging specific segments of the Salmonella chromosome with locked-in Mud-P22 prophages. Genetics. 1988 Apr;118(4):581–592. [PMC free article] [PubMed]
  • Benson NR, Goldman BS. Rapid mapping in Salmonella typhimurium with Mud-P22 prophages. J Bacteriol. 1992 Mar;174(5):1673–1681. [PMC free article] [PubMed]
  • Holden DW, Kronstad JW, Leong SA. Mutation in a heat-regulated hsp70 gene of Ustilago maydis. EMBO J. 1989 Jul;8(7):1927–1934. [PMC free article] [PubMed]
  • Sanger F, Nicklen S, Coulson AR. DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463–5467. [PMC free article] [PubMed]
  • Devereux J, Haeberli P, Smithies O. A comprehensive set of sequence analysis programs for the VAX. Nucleic Acids Res. 1984 Jan 11;12(1 Pt 1):387–395. [PMC free article] [PubMed]
  • Galán JE, Ginocchio C, Costeas P. Molecular and functional characterization of the Salmonella invasion gene invA: homology of InvA to members of a new protein family. J Bacteriol. 1992 Jul;174(13):4338–4349. [PMC free article] [PubMed]
  • Ginocchio C, Pace J, Galán JE. Identification and molecular characterization of a Salmonella typhimurium gene involved in triggering the internalization of salmonellae into cultured epithelial cells. Proc Natl Acad Sci U S A. 1992 Jul 1;89(13):5976–5980. [PMC free article] [PubMed]
  • Eichelberg K, Ginocchio CC, Galán JE. Molecular and functional characterization of the Salmonella typhimurium invasion genes invB and invC: homology of InvC to the F0F1 ATPase family of proteins. J Bacteriol. 1994 Aug;176(15):4501–4510. [PMC free article] [PubMed]
  • Collazo CM, Zierler MK, Galán JE. Functional analysis of the Salmonella typhimurium invasion genes invl and invJ and identification of a target of the protein secretion apparatus encoded in the inv locus. Mol Microbiol. 1995 Jan;15(1):25–38. [PubMed]
  • Ohara O, Dorit RL, Gilbert W. Direct genomic sequencing of bacterial DNA: the pyruvate kinase I gene of Escherichia coli. Proc Natl Acad Sci U S A. 1989 Sep;86(18):6883–6887. [PMC free article] [PubMed]
  • Bachmann BJ. Linkage map of Escherichia coli K-12, edition 8. Microbiol Rev. 1990 Jun;54(2):130–197. [PMC free article] [PubMed]
  • Liu SL, Hessel A, Sanderson KE. The XbaI-BlnI-CeuI genomic cleavage map of Salmonella typhimurium LT2 determined by double digestion, end labelling, and pulsed-field gel electrophoresis. J Bacteriol. 1993 Jul;175(13):4104–4120. [PMC free article] [PubMed]
  • Bergman T, Erickson K, Galyov E, Persson C, Wolf-Watz H. The lcrB (yscN/U) gene cluster of Yersinia pseudotuberculosis is involved in Yop secretion and shows high homology to the spa gene clusters of Shigella flexneri and Salmonella typhimurium. J Bacteriol. 1994 May;176(9):2619–2626. [PMC free article] [PubMed]
  • Andrews GP, Maurelli AT. mxiA of Shigella flexneri 2a, which facilitates export of invasion plasmid antigens, encodes a homolog of the low-calcium-response protein, LcrD, of Yersinia pestis. Infect Immun. 1992 Aug;60(8):3287–3295. [PMC free article] [PubMed]
  • Allaoui A, Sansonetti PJ, Parsot C. MxiD, an outer membrane protein necessary for the secretion of the Shigella flexneri lpa invasins. Mol Microbiol. 1993 Jan;7(1):59–68. [PubMed]
  • Venkatesan MM, Buysse JM, Oaks EV. Surface presentation of Shigella flexneri invasion plasmid antigens requires the products of the spa locus. J Bacteriol. 1992 Mar;174(6):1990–2001. [PMC free article] [PubMed]
  • Sasakawa C, Komatsu K, Tobe T, Suzuki T, Yoshikawa M. Eight genes in region 5 that form an operon are essential for invasion of epithelial cells by Shigella flexneri 2a. J Bacteriol. 1993 Apr;175(8):2334–2346. [PMC free article] [PubMed]
  • Plano GV, Barve SS, Straley SC. LcrD, a membrane-bound regulator of the Yersinia pestis low-calcium response. J Bacteriol. 1991 Nov;173(22):7293–7303. [PMC free article] [PubMed]
  • Michiels T, Vanooteghem JC, Lambert de Rouvroit C, China B, Gustin A, Boudry P, Cornelis GR. Analysis of virC, an operon involved in the secretion of Yop proteins by Yersinia enterocolitica. J Bacteriol. 1991 Aug;173(16):4994–5009. [PMC free article] [PubMed]
  • Kaniga K, Bossio JC, Galán JE. 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. [PubMed]
  • Ronson CW, Nixon BT, Ausubel FM. Conserved domains in bacterial regulatory proteins that respond to environmental stimuli. Cell. 1987 Jun 5;49(5):579–581. [PubMed]
  • Groisman EA, Sturmoski MA, Solomon FR, 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. [PMC free article] [PubMed]
  • Altmeyer RM, McNern JK, Bossio JC, Rosenshine I, Finlay BB, Galán JE. Cloning and molecular characterization of a gene involved in Salmonella adherence and invasion of cultured epithelial cells. Mol Microbiol. 1993 Jan;7(1):89–98. [PubMed]
  • Li J, Ochman H, Groisman EA, Boyd EF, Solomon F, Nelson K, Selander RK. 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. [PMC free article] [PubMed]
  • Fetherston JD, Schuetze P, Perry RD. 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. [PubMed]
  • Gouin E, Mengaud J, Cossart P. The virulence gene cluster of Listeria monocytogenes is also present in Listeria ivanovii, an animal pathogen, and Listeria seeligeri, a nonpathogenic species. Infect Immun. 1994 Aug;62(8):3550–3553. [PMC free article] [PubMed]
  • Hacker J, Bender L, Ott M, Wingender J, Lund B, Marre R, Goebel W. Deletions of chromosomal regions coding for fimbriae and hemolysins occur in vitro and in vivo in various extraintestinal Escherichia coli isolates. Microb Pathog. 1990 Mar;8(3):213–225. [PubMed]
  • 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. [PMC free article] [PubMed]
  • McDaniel TK, Jarvis KG, Donnenberg MS, Kaper JB. 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. [PMC free article] [PubMed]
  • Knapp S, Hacker J, Jarchau T, Goebel W. Large, unstable inserts in the chromosome affect virulence properties of uropathogenic Escherichia coli O6 strain 536. J Bacteriol. 1986 Oct;168(1):22–30. [PMC free article] [PubMed]
  • Finlay BB, Ruschkowski S, Dedhar S. Cytoskeletal rearrangements accompanying salmonella entry into epithelial cells. J Cell Sci. 1991 Jun;99(Pt 2):283–296. [PubMed]
  • Francis CL, Starnbach MN, Falkow S. Morphological and cytoskeletal changes in epithelial cells occur immediately upon interaction with Salmonella typhimurium grown under low-oxygen conditions. Mol Microbiol. 1992 Nov;6(21):3077–3087. [PubMed]

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

Formats:

Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...

Links

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...