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Emerg Infect Dis. 1996 Oct-Dec; 2(4): 270–288.
PMCID: PMC2639918

Molecular mechanisms of bacterial virulence: type III secretion and pathogenicity islands.

Abstract

Recently, two novel but widespread themes have emerged in the field of bacterial virulence: type III secretion systems and pathogenicity islands. Type III secretion systems, which are found in various gram-negative organisms, are specialized for the export of virulence factors delivered directly to host cells. These factors subvert normal host cell functions in ways that seem beneficial to invading bacteria. The genes encoding several type III secretion systems reside on pathogenicity islands, which are inserted DNA segments within the chromosome that confer upon the host bacterium a variety of virulence traits, such as the ability to acquire iron and to adhere to or enter host cells. Many of these segments of DNA appear to have been acquired in a single step from a foreign source. The ability to obtain complex virulence traits in one genetic event, rather than by undergoing natural selection for many generations, provides a mechanism for sudden radical changes in bacterial-host interactions. Type III secretion systems and pathogenicity islands must have played critical roles in the evolution of known pathogens and are likely to lead to the emergence of novel infectious diseases in the future.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Finlay BB, Falkow S. Common themes in microbial pathogenicity. Microbiol Rev. 1989 Jun;53(2):210–230. [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]
  • Fenselau S, Balbo I, Bonas U. Determinants of pathogenicity in Xanthomonas campestris pv. vesicatoria are related to proteins involved in secretion in bacterial pathogens of animals. Mol Plant Microbe Interact. 1992 Sep-Oct;5(5):390–396. [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]
  • 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]
  • 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. [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]
  • 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]
  • Haddix PL, Straley SC. Structure and regulation of the Yersinia pestis yscBCDEF operon. J Bacteriol. 1992 Jul;174(14):4820–4828. [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]
  • Michiels T, Wattiau P, Brasseur R, Ruysschaert JM, Cornelis G. Secretion of Yop proteins by Yersiniae. Infect Immun. 1990 Sep;58(9):2840–2849. [PMC free article] [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]
  • Rosqvist R, Forsberg A, Wolf-Watz H. Intracellular targeting of the Yersinia YopE cytotoxin in mammalian cells induces actin microfilament disruption. Infect Immun. 1991 Dec;59(12):4562–4569. [PMC free article] [PubMed]
  • 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. [PubMed]
  • Ménard R, Prévost MC, Gounon P, Sansonetti P, Dehio C. The secreted Ipa complex of Shigella flexneri promotes entry into mammalian cells. Proc Natl Acad Sci U S A. 1996 Feb 6;93(3):1254–1258. [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]
  • Watarai M, Tobe T, Yoshikawa M, Sasakawa C. Contact of Shigella with host cells triggers release of Ipa invasins and is an essential function of invasiveness. EMBO J. 1995 Jun 1;14(11):2461–2470. [PMC free article] [PubMed]
  • Pugsley AP. The complete general secretory pathway in gram-negative bacteria. Microbiol Rev. 1993 Mar;57(1):50–108. [PMC free article] [PubMed]
  • Fath MJ, Kolter R. ABC transporters: bacterial exporters. Microbiol Rev. 1993 Dec;57(4):995–1017. [PMC free article] [PubMed]
  • Stephens C, Shapiro L. Delivering the payload. Bacterial pathogenesis. Curr Biol. 1996 Aug 1;6(8):927–930. [PubMed]
  • Aizawa SI. Flagellar assembly in Salmonella typhimurium. Mol Microbiol. 1996 Jan;19(1):1–5. [PubMed]
  • Harshey RM, Toguchi A. Spinning tails: homologies among bacterial flagellar systems. Trends Microbiol. 1996 Jun;4(6):226–231. [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]
  • Ménard R, Sansonetti P, Parsot C. The secretion of the Shigella flexneri Ipa invasins is activated by epithelial cells and controlled by IpaB and IpaD. EMBO J. 1994 Nov 15;13(22):5293–5302. [PMC free article] [PubMed]
  • Rosqvist R, Magnusson KE, 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. [PMC free article] [PubMed]
  • Galán JE. Molecular genetic bases of Salmonella entry into host cells. Mol Microbiol. 1996 Apr;20(2):263–271. [PubMed]
  • Straley SC, Perry RD. Environmental modulation of gene expression and pathogenesis in Yersinia. Trends Microbiol. 1995 Aug;3(8):310–317. [PubMed]
  • Hromockyj AE, Tucker SC, Maurelli AT. Temperature regulation of Shigella virulence: identification of the repressor gene virR, an analogue of hns, and partial complementation by tyrosyl transfer RNA (tRNA1(Tyr)). Mol Microbiol. 1992 Aug;6(15):2113–2124. [PubMed]
  • Pettersson J, Nordfelth R, Dubinina E, Bergman T, Gustafsson M, Magnusson KE, Wolf-Watz H. Modulation of virulence factor expression by pathogen target cell contact. Science. 1996 Aug 30;273(5279):1231–1233. [PubMed]
  • Kenny B, Lai LC, Finlay BB, Donnenberg MS. EspA, a protein secreted by enteropathogenic Escherichia coli, is required to induce signals in epithelial cells. Mol Microbiol. 1996 Apr;20(2):313–323. [PubMed]
  • 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. [PubMed]
  • Håkansson S, Galyov EE, Rosqvist R, Wolf-Watz H. The Yersinia YpkA Ser/Thr kinase is translocated and subsequently targeted to the inner surface of the HeLa cell plasma membrane. Mol Microbiol. 1996 May;20(3):593–603. [PubMed]
  • Sory MP, Cornelis GR. Translocation of a hybrid YopE-adenylate cyclase from Yersinia enterocolitica into HeLa cells. Mol Microbiol. 1994 Nov;14(3):583–594. [PubMed]
  • Ménard R, Dehio C, Sansonetti PJ. Bacterial entry into epithelial cells: the paradigm of Shigella. Trends Microbiol. 1996 Jun;4(6):220–226. [PubMed]
  • Jones B, Pascopella L, Falkow S. Entry of microbes into the host: using M cells to break the mucosal barrier. Curr Opin Immunol. 1995 Aug;7(4):474–478. [PubMed]
  • Shea JE, Hensel M, Gleeson C, Holden DW. Identification of a virulence locus encoding a second type III secretion system in Salmonella typhimurium. Proc Natl Acad Sci U S A. 1996 Mar 19;93(6):2593–2597. [PMC free article] [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]
  • Rosqvist R, Håkansson S, Forsberg A, Wolf-Watz H. Functional conservation of the secretion and translocation machinery for virulence proteins of yersiniae, salmonellae and shigellae. EMBO J. 1995 Sep 1;14(17):4187–4195. [PMC free article] [PubMed]
  • Hermant D, Ménard R, Arricau N, Parsot C, Popoff MY. Functional conservation of the Salmonella and Shigella effectors of entry into epithelial cells. Mol Microbiol. 1995 Aug;17(4):781–789. [PubMed]
  • Woestyn S, Allaoui A, Wattiau P, Cornelis GR. YscN, the putative energizer of the Yersinia Yop secretion machinery. J Bacteriol. 1994 Mar;176(6):1561–1569. [PMC free article] [PubMed]
  • Plano GV, Straley SC. Mutations in yscC, yscD, and yscG prevent high-level expression and secretion of V antigen and Yops in Yersinia pestis. J Bacteriol. 1995 Jul;177(13):3843–3854. [PMC free article] [PubMed]
  • Allaoui A, Woestyn S, Sluiters C, Cornelis GR. YscU, a Yersinia enterocolitica inner membrane protein involved in Yop secretion. J Bacteriol. 1994 Aug;176(15):4534–4542. [PMC free article] [PubMed]
  • Fields KA, Plano GV, Straley SC. A low-Ca2+ response (LCR) secretion (ysc) locus lies within the lcrB region of the LCR plasmid in Yersinia pestis. J Bacteriol. 1994 Feb;176(3):569–579. [PMC free article] [PubMed]
  • Allaoui A, Schulte R, Cornelis GR. Mutational analysis of the Yersinia enterocolitica virC operon: characterization of yscE, F, G, I, J, K required for Yop secretion and yscH encoding YopR. Mol Microbiol. 1995 Oct;18(2):343–355. [PubMed]
  • Allaoui A, Scheen R, Lambert de Rouvroit C, Cornelis GR. VirG, a Yersinia enterocolitica lipoprotein involved in Ca2+ dependency, is related to exsB of Pseudomonas aeruginosa. J Bacteriol. 1995 Aug;177(15):4230–4237. [PMC free article] [PubMed]
  • Rimpiläinen M, Forsberg A, Wolf-Watz H. A novel protein, LcrQ, involved in the low-calcium response of Yersinia pseudotuberculosis shows extensive homology to YopH. J Bacteriol. 1992 May;174(10):3355–3363. [PMC free article] [PubMed]
  • Håkansson S, Bergman T, Vanooteghem JC, Cornelis G, Wolf-Watz H. YopB and YopD constitute a novel class of Yersinia Yop proteins. Infect Immun. 1993 Jan;61(1):71–80. [PMC free article] [PubMed]
  • Wattiau P, Woestyn S, Cornelis GR. Customized secretion chaperones in pathogenic bacteria. Mol Microbiol. 1996 Apr;20(2):255–262. [PubMed]
  • Frithz-Lindsten E, Rosqvist R, Johansson L, Forsberg A. The chaperone-like protein YerA of Yersinia pseudotuberculosis stabilizes YopE in the cytoplasm but is dispensible for targeting to the secretion loci. Mol Microbiol. 1995 May;16(4):635–647. [PubMed]
  • Ménard R, Sansonetti P, Parsot C, Vasselon T. Extracellular association and cytoplasmic partitioning of the IpaB and IpaC invasins of S. flexneri. Cell. 1994 Nov 4;79(3):515–525. [PubMed]
  • Skryzpek E, Straley SC. LcrG, a secreted protein involved in negative regulation of the low-calcium response in Yersinia pestis. J Bacteriol. 1993 Jun;175(11):3520–3528. [PMC free article] [PubMed]
  • Forsberg A, Viitanen AM, Skurnik M, Wolf-Watz H. The surface-located YopN protein is involved in calcium signal transduction in Yersinia pseudotuberculosis. Mol Microbiol. 1991 Apr;5(4):977–986. [PubMed]
  • Hughes KT, Gillen KL, Semon MJ, Karlinsey JE. Sensing structural intermediates in bacterial flagellar assembly by export of a negative regulator. Science. 1993 Nov 19;262(5137):1277–1280. [PubMed]
  • Ginocchio CC, Galán JE. Functional conservation among members of the Salmonella typhimurium InvA family of proteins. Infect Immun. 1995 Feb;63(2):729–732. [PMC free article] [PubMed]
  • Jarvis KG, Girón JA, Jerse AE, McDaniel TK, Donnenberg MS, Kaper JB. 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. [PMC free article] [PubMed]
  • Ochman H, Groisman EA. The evolution of invasion by enteric bacteria. Can J Microbiol. 1995 Jul;41(7):555–561. [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]
  • Morschhäuser J, Vetter V, Emödy L, Hacker J. Adhesin regulatory genes within large, unstable DNA regions of pathogenic Escherichia coli: cross-talk between different adhesin gene clusters. Mol Microbiol. 1994 Feb;11(3):555–566. [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]
  • Stein MA, Leung KY, Zwick M, Garcia-del Portillo F, Finlay BB. Identification of a Salmonella virulence gene required for formation of filamentous structures containing lysosomal membrane glycoproteins within epithelial cells. Mol Microbiol. 1996 Apr;20(1):151–164. [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]
  • Fetherston JD, Perry RD. The pigmentation locus of Yersinia pestis KIM6+ is flanked by an insertion sequence and includes the structural genes for pesticin sensitivity and HMWP2. Mol Microbiol. 1994 Aug;13(4):697–708. [PubMed]
  • Iteman I, Guiyoule A, de Almeida AM, Guilvout I, Baranton G, Carniel E. Relationship between loss of pigmentation and deletion of the chromosomal iron-regulated irp2 gene in Yersinia pestis: evidence for separate but related events. Infect Immun. 1993 Jun;61(6):2717–2722. [PMC free article] [PubMed]
  • Rakin A, Urbitsch P, Heesemann J. Evidence for two evolutionary lineages of highly pathogenic Yersinia species. J Bacteriol. 1995 May;177(9):2292–2298. [PMC free article] [PubMed]
  • Matic I, Taddei F, Radman M. Genetic barriers among bacteria. Trends Microbiol. 1996 Feb;4(2):69–72. [PubMed]
  • Waldor MK, Mekalanos JJ. Lysogenic conversion by a filamentous phage encoding cholera toxin. Science. 1996 Jun 28;272(5270):1910–1914. [PubMed]
  • Guttman DS, Dykhuizen DE. Clonal divergence in Escherichia coli as a result of recombination, not mutation. Science. 1994 Nov 25;266(5189):1380–1383. [PubMed]
  • Inouye S, Sunshine MG, Six EW, 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. [PubMed]
  • Reiter WD, Palm P, Yeats S. Transfer RNA genes frequently serve as integration sites for prokaryotic genetic elements. Nucleic Acids Res. 1989 Mar 11;17(5):1907–1914. [PMC free article] [PubMed]
  • Sun J, Inouye M, Inouye S. Association of a retroelement with a P4-like cryptic prophage (retronphage phi R73) integrated into the selenocystyl tRNA gene of Escherichia coli. J Bacteriol. 1991 Jul;173(13):4171–4181. [PMC free article] [PubMed]
  • Akerley BJ, Cotter PA, Miller JF. Ectopic expression of the flagellar regulon alters development of the Bordetella-host interaction. Cell. 1995 Feb 24;80(4):611–620. [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]
  • Ritter A, Blum G, Emödy L, Kerenyi M, Böck A, Neuhierl B, Rabsch W, Scheutz F, Hacker J. tRNA genes and pathogenicity islands: influence on virulence and metabolic properties of uropathogenic Escherichia coli. Mol Microbiol. 1995 Jul;17(1):109–121. [PubMed]
  • Zagaglia C, Casalino M, Colonna B, Conti C, Calconi A, Nicoletti M. Virulence plasmids of enteroinvasive Escherichia coli and Shigella flexneri integrate into a specific site on the host chromosome: integration greatly reduces expression of plasmid-carried virulence genes. Infect Immun. 1991 Mar;59(3):792–799. [PMC free article] [PubMed]
  • Colonna B, Casalino M, Fradiani PA, Zagaglia C, Naitza S, Leoni L, Prosseda G, Coppo A, Ghelardini P, Nicoletti M. H-NS regulation of virulence gene expression in enteroinvasive Escherichia coli harboring the virulence plasmid integrated into the host chromosome. J Bacteriol. 1995 Aug;177(16):4703–4712. [PMC free article] [PubMed]
  • Zsigray RM, Hopper JB, Zukowski K, Chesbro WR. Integration of the Vwa plasmid into the chromosome of Yersinia pestis strains harboring F' plasmids of Escherichia coli. Infect Immun. 1985 Mar;47(3):670–673. [PMC free article] [PubMed]
  • Zsigray RM, Lawton WD, Surgalla MJ. Repression of the virulence of Yersinia pestis by an F' plasmid. Infect Immun. 1983 Feb;39(2):974–976. [PMC free article] [PubMed]
  • Protsenko OA, Filippov AA, Kutyrev VV. Integration of the plasmid encoding the synthesis of capsular antigen and murine toxin into Yersinia pestis chromosome. Microb Pathog. 1991 Aug;11(2):123–128. [PubMed]
  • Whittam TS, Wolfe ML, Wachsmuth IK, Orskov F, Orskov I, Wilson RA. Clonal relationships among Escherichia coli strains that cause hemorrhagic colitis and infantile diarrhea. Infect Immun. 1993 May;61(5):1619–1629. [PMC free article] [PubMed]
  • Waldor MK, Mekalanos JJ. Vibrio cholerae O139 specific gene sequences. Lancet. 1994 May 28;343(8909):1366–1366. [PubMed]
  • Pajni S, Sharma C, Bhasin N, Ghosh A, Ramamurthy T, Nair GB, Ramajayam S, Das B, Kar S, Roychowdhury S, et al. Studies on the genesis of Vibrio cholerae O139: identification of probable progenitor strains. J Med Microbiol. 1995 Jan;42(1):20–25. [PubMed]
  • Bik EM, Bunschoten AE, Gouw RD, Mooi FR. Genesis of the novel epidemic Vibrio cholerae O139 strain: evidence for horizontal transfer of genes involved in polysaccharide synthesis. EMBO J. 1995 Jan 16;14(2):209–216. [PMC free article] [PubMed]
  • Falkow S, Small P, Isberg R, Hayes SF, Corwin D. A molecular strategy for the study of bacterial invasion. Rev Infect Dis. 1987 Sep-Oct;9 (Suppl 5):S450–S455. [PubMed]
  • Swenson DL, Bukanov NO, Berg DE, Welch RA. Two pathogenicity islands in uropathogenic Escherichia coli J96: cosmid cloning and sample sequencing. Infect Immun. 1996 Sep;64(9):3736–3743. [PMC free article] [PubMed]
  • Blum G, Falbo V, Caprioli A, Hacker J. Gene clusters encoding the cytotoxic necrotizing factor type 1, Prs-fimbriae and alpha-hemolysin form the pathogenicity island II of the uropathogenic Escherichia coli strain J96. FEMS Microbiol Lett. 1995 Feb 15;126(2):189–195. [PubMed]
  • Comstock LE, Johnson JA, Michalski JM, Morris JG, Jr, Kaper JB. Cloning and sequence of a region encoding a surface polysaccharide of Vibrio cholerae O139 and characterization of the insertion site in the chromosome of Vibrio cholerae O1. Mol Microbiol. 1996 Feb;19(4):815–826. [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]

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