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1 - Invasion mechanisms of Salmonella

Published online by Cambridge University Press:  21 August 2009

Beth A. McCormick
Affiliation:
Department of Pediatric Gastroenterology and Nutrition, Mucosal Immunology Laboratory, Massachusetts General Hospital, Charlestown, Massachusetts 02129-4404, USA
Richard J. Lamont
Affiliation:
University of Florida
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Summary

Salmonella enterica serovar Typhimurium is a facultative intracellular pathogen that causes gastroenteritis in humans and a systemic disease similar to typhoid fever in mice. Following oral ingestion, bacteria colonize the intestinal tract and then penetrate the lymphatic and blood circulation systems. Passage of eukaryotic organisms through the intestinal epithelium is thought to be initiated by bacterial invasion into M cells and enterocytes. The process of epithelial cell invasion can be studied experimentally because S. enterica serovar Typhimurium invades cultured epithelial cells in vitro. Many of the genes required for epithelial invasion have been found within eukaryotic pathogenicity island 1 (SPI-1), which is a contiguous 40-kb region at centrosome 63 of the chromosome. SPI-1 genes encode a bacterial type III secretion apparatus and several effectors, which contribute to pathogenesis through an interaction with eukaryotic proteins. The type III secretion apparatus is a multiprotein complex that is thought to build a contiguous channel across both the bacterial and epithelial cell membranes, resulting in efficient translocation of bacterial effectors directly into the cytosol of epithelial cells. The secreted effectors are thought to interact with eukaryotic proteins to activate signal transduction pathways and rearrange the actin cytoskeleton, leading to membrane ruffling and engulfment of the bacterium. This chapter discusses the mechanism by which S. typhimurium enter into host cells.

CLINICAL DESCRIPTION

S. enterica, gram-negative bacteria of the family Enterobacteriaceae, cause a variety of diseases in humans and other animal hosts.

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Publisher: Cambridge University Press
Print publication year: 2004

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References

Ahmer, B. M., Reeuwijk, J., Watsom, P. R., Wallis, T. S., and Heffron, F. (1999). Salmonella SirA is a globalregulator of genes mediating enteropathogenesis. Mol. Microbiol. 31, 971–982CrossRefGoogle ScholarPubMed
Bakshi, C. S., Singh, V. P., Wood, M. W., Jones, P. W., Wallis, T. S., and Galyov, E. E. (2000). Identification of SopE2, a Salmonella secreted protein which is highly homologous to SopE and involved in bacterial invasion of epithelial cells. J. Bacteriol. 182, 2341–2344CrossRefGoogle ScholarPubMed
Bolton, A. J., Osborne, M. P., Wallis, T. S., and Stephen, J. (1999). Interaction of Salmonella choleraesuis, Salmonella dublin, and Salmonella typhimurium with porcine and bovine terminal ileum in vivo. Microbiology 145, 2431–2441CrossRefGoogle ScholarPubMed
Buchwald, G., Friebel, A., Galan, J. E., Hardt, W. D., Wittinghofer, A., and Scheffzek, K. (2002). Structural basis for the reversible activation of a Rho protein by the bacterial toxin SopE. EMBO J. 21, 3286–3295CrossRefGoogle ScholarPubMed
Carlson, S. A. and Jones, B. D. (1998). Inhibition of Salmonella typhimurium invasion by host cell expression of secreted bacterial invasion proteins. Infect. Immun. 66, 5295–5300Google ScholarPubMed
Caron, E. and Hall, A. (1998). Identification of two distinct mechanisms of phagocytosis controlled by different GTPases. Science 282, 1717–1721CrossRefGoogle Scholar
Carter, P. B. and Collins, F. M. (1974). The route of enteric infection in normal mice. J. Exp. Med. 139, 1189–1203CrossRefGoogle ScholarPubMed
Chen, L.-M., Hobbie, S., and Galan, J. E. (1996). Requirement of CDC42 for Salmonella-induced cytoskeletal and nuclear responses. Science 274, 2115–2118CrossRefGoogle ScholarPubMed
Cirillo, D. M., Valdivia, R. H., Monack, D. M., and Falkow, S. (1998). Macrophage-dependent induction of the Salmonella pathogenicity island 2 type III secretion system and its role in intracellular survival. Mol. Microbiol. 30, 175–188CrossRefGoogle ScholarPubMed
Collazo, C. M. and Galan, J. E. (1997). The invasion-associated type III system of Salmonella typhimurium directs the translocation of Sip proteins into the host cell. Mol. Microbiol. 24, 747–756CrossRefGoogle ScholarPubMed
Cox, D., Chang, P., Zhang, Q, Reddy, P. G., Bokoch, G. M., and Greenberg, S. (1997). Requirement for both Rac1 and Cdc42 in membrane ruffling and phagocytosis in leukocytes. J. Exp. Med. 186, 1487–1494CrossRefGoogle Scholar
Criss, A. K., Ahlgren, D. M., Jou, T-S., McCormick, B. A., and Casanova, J. E. (2001). The GTPase Rac1 selectively regulates Salmonella invasion at the apical plasma membrane of polarized epithelial cells. J. Cell Sci. 114, 1331–1341Google ScholarPubMed
Criss, A. K. and Casanova, J. E. (2003). Coordinate regulation of Salmonella enterica serovar Typhimurium invasion of epithelial cells by the Arp 2/3 complexand Rho GTPases. Infect. Immun. 71, 2885–2891CrossRefGoogle Scholar
Criss, A. K., Silva, M., Casanova, J. E., and McCormick, B. A. (2001). Regulation of Salmonella-induced neutrophil transmigration by epithelial ADP-ribosylation factor 6. J. Biol. Chem. 276, 48,431–48,439CrossRefGoogle ScholarPubMed
Darwin, K. H. and Miller, V. L. (1999a). Molecular basis of the interaction of Salmonella with the intestinal mucosa. Clin. Microbiol. Rev. 12, 405–428Google Scholar
Darwin, K. H. and Miller, V. L. (1999b). InvF is required for expression of genes encoding proteins secreted by the SPI1 type III secretion apparatus in Salmonella typhimurium. J. Bacteriol. 181, 4949–4954Google Scholar
Eichelberg, K., Ginocchio, C. C., and Galan, J. E. (1994). Molecular and functional characterization of the Salmonella typhimurium invasion genes invB and invC: homology of InvC to the FOF1 ATPase family of proteins. J. Bacteriol. 176, 4501–4510CrossRefGoogle Scholar
Fath, K. R., Mamajiwalla, S. N., and Burgess, D. R. (1993). The cytoskeleton in development of epithelial cell polarity. J. Cell Sci. Suppl. 17, 65–73CrossRefGoogle ScholarPubMed
Finlay, B. B. and Falkow, S. (1988). Comparison of the invasion strategies used by Salmonella cholerae-suis, Shigella flexneri and Yersinia enterocolitica to enter cultured animal cells: endosome acidification is not required for bacterial invasion or intracellular replication. Biochimie. 70, 1089–1099CrossRefGoogle ScholarPubMed
Finlay, B. B. and Falkow, S. (1990). Salmonella interactions with polarized human intestinal Caco-2 epithelial cells. J. Infect. Dis. 162, 1096–1106CrossRefGoogle ScholarPubMed
Finlay, B. B., Gumbiner, B., and Falkow, S. (1988). Penetration of Salmonella through a polarized Madin-Darby canine kidney epithelial cell monolayer. J. Cell Biol. 107, 221–230CrossRefGoogle ScholarPubMed
Finlay, B. B., Ruschkowski, S., and Dedhar, S. (1991). Cytoskeletal rearrangements accompanying Salmonella entry into epithelial cells. J. Cell Sci. 99, 283–296Google ScholarPubMed
Francis, C. L., Ryan, T. A., Jones, B. D., Smith, S. J., and Falkow, S. (1993). Ruffles induced by Salmonella and other stimuli direct macropinocytosis of bacteria. Nature 364, 639–642CrossRefGoogle Scholar
Fu, Y. and Galan, J. E. (1998). Identification of a specific chaperone for SptP, a substrate of the centrisome 63 type III secretion system of Salmonella typhimurium. J. Bacteriol. 180, 3393–3399Google ScholarPubMed
Fu, Y. and Galan, J. E. (1999). A Salmonella protein antagonizes Rac-1 and cdc42 to mediate host recovery after bacterial invasion. Nature 401, 293–297CrossRefGoogle ScholarPubMed
Galan, J. E. and Curtiss, R. (1989). Cloning and molecular characterization of genes whose products allow Salmonella typhimurium to penetrate tissue culture cells. Proc. Natl. Acad. Sci. USA 86, 6383–6387CrossRefGoogle ScholarPubMed
Galyov, E. G., Wood, M. W., Rosqvist, R., Mullan, P. B., Watson, P. R., Hedges, S., and Wallis, T. S. (1997). A secreted effector protein of Salmonella dublin is translocated into eukaryotic cells and mediates inflammation and fluid secretion in infected ileal mucosa. Mol. Microbiol. 25, 903–912CrossRefGoogle ScholarPubMed
Hall, A. (1998). Rho GTPases and the actin cytoskeleton. Science 270, 509–514CrossRefGoogle Scholar
Hansen-Wester, I. and Hensel, M. (2001). Salmonella pathogenicity island encoding type III effector systems. Microbes Infect. 3, 549–559CrossRefGoogle Scholar
Hardt, W. D., Chen, L. M., Schuebel, K. E., Bustelo, X. R., and Galan, J. E. (1998). S. typhimurium encodes an activator of Rho GTPases that induces membrane ruffling and nuclear responses in host cells. Cell 93, 815–826CrossRefGoogle ScholarPubMed
Hayward, R. D. and Koronakis, V. (1999). Direct nucleation and bundling of actin by the SipC protein of invasive Salmonella. EMBO J. 18, 4926–4934CrossRefGoogle ScholarPubMed
Hensel, M., Shea, J. E., Waterman, S. R., Mundy, R., Nikolaus, T., Banks, G., Vazquez-Torres, A., Gleeson, C., Fang, F. C., and Holden, D. W. (1998). Genes encoding putative effector proteins of the type III secretion system of Salmonella pathogenicity island 2 are required for bacterial virulence and proliferation in macrophages. Mol. Microbiol. 30, 163–174CrossRefGoogle ScholarPubMed
Hermant, D., Menard, R., Arricau, N., Parsot, C., and Popoff, M. Y. (1995). Functional conservation of the Salmonella and Shigella effectors of entry into epithelial cells. Mol. Microbiol. 17, 781–789CrossRefGoogle ScholarPubMed
Hohmann, E. L. (2001). Nontyphoidal salmonellosis. Clin. Infect. Dis. 32, 263–269Google ScholarPubMed
Hook, E. W., (1990). Salmonella species (including typhoid fever). In Principles and Practice of Infectious Diseases, ed. G. L. Mandell, R. G. Douglas, and J. E. Bennet, pp. 1700–1716. New York: Churchill Livingstone
Kaniga, K., Uralil, J., Bliska, J. B., and Galan, J. E. (1996). A secreted tyrosine phosphate with modular effector domains in the bacterial pathogen Salmonella typhimurium. Mol. Microbiol. 21, 633–641CrossRefGoogle Scholar
Kozma, R., Ahmed, S., Best, A., and Lim, V. (1995). The Ras-related protein Cdc42Hs and bradykinin promote formation of peripheral actin microspikes and filopodia in Swiss 3T3 fibroblasts. Mol. Cell. Biol. 15, 1942–1952CrossRefGoogle ScholarPubMed
Kubori, T., Matsushima, Y., Nakamura, D., Uralil, J., Lara-Tejero, M., Sukhan, A., Galan, J. E., and Aizawa, S. I. (1998). Supramolecular structure of the Salmonella typhimurium type III protein secretion system. Science 280, 602–605CrossRefGoogle ScholarPubMed
Kubori, T., Sukhan, A., Aizawa, S. I., and Galan, J. E. (2000). Molecular characterization and assembly of the needle complex of the Salmonella typhimurium type III protein secretion system. Proc. Natl. Acad. Sci. USA 97, 10,225–10,230CrossRefGoogle ScholarPubMed
Lee, C. A. and Falkow, S. (1990). The ability of Salmonella to enter mammalian cells is affected by bacteria growth state. Proc. Natl. Acad. Sci. USA 87, 4304–4308CrossRefGoogle ScholarPubMed
Lee, C. A., Silva, M., Siber, A. M., Kelly, A. J., Galyov, E., and McCormick, B. A. (2000). A secreted Salmonella protein induces a proinflammatory response in epithelial cells, which promotes neutrophil migration. Proc. Natl. Acad. Sci. USA 97, 12,283–12,288CrossRefGoogle ScholarPubMed
Li, J., Ochman, H., Groisman, E. A., Boyd, E. F., Solomon, F., Nelson, K., and Selander, R. K. (1995). Relationship between evolutionary rate and cellular location among the Inv/Spa invasion proteins of Salmonella enterica. Proc. Natl. Acad. Sci. USA 92, 7252–7256CrossRefGoogle ScholarPubMed
Lostroh, C. P., Bajaj, V., and Lee, C. A. (2000). The cis requirement for transcriptional activation by HilA, a virulence determinant encoded on SPI1. Mol. Microbiol. 37, 300–315CrossRefGoogle Scholar
Lucas, R. L. and Lee, C. A. (2001). Roles of hilC and hilD in regulation of hilA expression in Salmonella enterica serovar typhimurium. J. Bacteriol. 183, 2733–2745CrossRefGoogle ScholarPubMed
Massol, P., Montcourrier, P., Guilemot, J. C., and Chavier, P. (1998). Fc receptor-mediated phagocytosis requires CDC42 and Rac1. EMBO J. 17, 6219–6229CrossRefGoogle ScholarPubMed
McGhie, E. J., Hayward, R. D., and Koronakis, V. (2001). Cooperation between actin-binding proteins of invasive Salmonella SipA potentiates SipC nucleation and bundling of actin. EMBO J. 20, 2131–2139CrossRefGoogle ScholarPubMed
Mills, D. M., Bajaj, V., and Lee, C. A. (1995). A 40 kb chromosomal fragment encoding Salmonella typhimurium invasion genes is absent from the corresponding region of the Escherichia K-12 chromosome. Mol. Microbiol. 15, 749–759CrossRefGoogle Scholar
Mills, S. D. and Finlay, B. B. (1994). Comparison of Salmonella typhi and Salmonella typhimurium invasion, intracellular growth and localization in cultured human epithelial cells. Microb. Pathog. 17, 409–423CrossRefGoogle ScholarPubMed
Mirold, S., Rabsch, W., Rohde, M., Stender, S., Tschape, H., Russmann, H., Igwe, E., and Hardt, W. D. (1999). Isolation of a temperate bacteriophage encoding the type III effector protein SopE from an epidemic Salmonella typhimurium strain. Proc. Natl. Acad. Sci.USA 96, 9845–9850CrossRefGoogle ScholarPubMed
Murli, S., Watson, R. O., and Galan, J. E. (2001). Role of tyrosine kinases and the tyrosine phosphatase SptP in the interaction of Salmonella with host cells. Cell. Microbiol. 3, 795–810CrossRefGoogle ScholarPubMed
Murray, R. A. and Lee, C. A. (2000). Invasion genes are not required for Salmonella enterica serovar typhimurium to breach the intestinal epithelium: evidence that Salmonella pathogenicity island 1 has alternative functions during infection. Infect. Immun. 68, 5050–5055CrossRefGoogle Scholar
Nobes, C. D. and Hall, A. (1995). Rho, Rac, and Cdc42 GTPases regulate the assembly of multimolecular focal adhesion complexes associated with actin stress fibers, lamellipodia and filopodia. Cell 81, 53–62CrossRefGoogle ScholarPubMed
Penheiter, K. L., Mathur, N., Giles, D., Fahlen, T., and Jones, B. D. (1997). Non-invasive Salmonella typhimurium mutants are avirulent because of an inability to enter and destroy M cells of ileal Peyer's patches. Mol. Microbiol. 24, 697–709CrossRefGoogle ScholarPubMed
Rescigno, M., Urbano, M., Valzasina, B., Francolini, M., Rotta, G., Bonasio, R., Granucci, F., Kraehenbuhl, J-P., and Ricciardi-Castagnoli, P. (2001). Dendritic cells express tight junction proteins and penetrate gut epithelial monolayers to sample bacteria. Nature Immunol. 2, 361–367CrossRefGoogle ScholarPubMed
Ridley, A. J. and Hall, A. (1992). The small GTPase binding protein rho regulates the assembly of focal adhesions and actin stress fibers in response to growth factors. Cell 70, 389–399CrossRefGoogle ScholarPubMed
Rosqvist, R., Hakansson, S., Forsberg, A., and Wolf-Watz, H. (1995). Functional conservation of the secretion and translocation machinery for virulence proteins of Yersiniae, Salmonellae, and Shigellae. EMBO J. 14, 4187–4195Google ScholarPubMed
Rout, W. R., Formal, S. B., Dammin, G. J., and Giannella, R. A. (1974). Pathophysiology of Salmonella diarrhea in the Rhesus monkey: intestinal transport, morphological and bacteriological studies. Gastroenterology 67, 59–70Google ScholarPubMed
Rudolph, M. G., Weise, C., Mirold, S., Hillenbrand, B., Bader, B., Wittinghofer, A., and Hardt, W. D. (1999). Biochemical analysis of SopE from Salmonella typhimurium, a highly efficient guanosine nucleotide exchange factor for Rho GTPases. J. Biol. Chem. 274, 30,501–30,509CrossRefGoogle Scholar
Shea, J. E., Beuzon, C. R., Gleeson, C., Mundy, R., and Holden, D. W. (1999). Influence of the Salmonella typhimurium pathogenicity island 2 type III secretion system on bacterial growth in the mouse. Infect. Immun. 67, 213–219Google ScholarPubMed
Stender, S., Friebel, A., Linder, S., Rohde, M., Mirold, S., and Hardt, W. D. (2000). Identification of SopE2 from Salmonella typhimurium, a conserved guanine nucleotide exchange factor for Cdc42 of the host cell. Mol. Microbiol. 36, 1206–1221CrossRefGoogle ScholarPubMed
Takeuchi, A. (1967). Electron microscope studies of experimental Salmonella infection. I. Penetration into the intestinal epithelium by Salmonella typhimurium. Am. J. Pathol. 50, 109–136Google ScholarPubMed
Uchiya, K., Barbieri, M. A., Funato, K., Shah, A. H., Stahl, P. D., and Groisman, E. A. (1999). A Salmonella virulence protein that inhibits cellular traffickingEMBO J. 18, 3926–393CrossRefGoogle ScholarPubMed
Aelst, L. and D'Souza-Schorey, C. (1997). Rho GTPases and signaling networks. Genes Dev. 11, 2295–2322CrossRefGoogle ScholarPubMed
Vazquez-Torres, A., Jones-Carson, J., Mastroeni, P., Ischiropoulos, H., and Fang, F. C. (2000). Antimicrobial actions of the NADPH phagocyte oxidase and inducible nitric oxide synthase in experimental salmonellosis. I. Effects on microbial killing by activated peritoneal macrophages in vitro. J. Exp. Med. 192, 227–236CrossRefGoogle ScholarPubMed
Vazquez-Torres, A., Jones-Carson, J., Baumler, A. J., Falkow, S., Valdivia, R., Brown, W., Le, M., Berggren, R., Parkos, W. T., and Fang, F. C. (1999). Extraintestinal dissemination of Salmonella by CD-18-expressing phagocytes. Nature 401, 804–808Google ScholarPubMed
Wallis, T. S. and Galyov, E. E. (2000). Molecular basis of Salmonella-induced enteritis. Mol. Microbiol. 36, 997–1005CrossRefGoogle ScholarPubMed
Watson, P. R., Paulin, S. M., Bland, A. P., Jones, P. W., and Wallis, T. S. (1995). Characterization of intestinal invasion by Salmonella typhimurium and Salmonella dublin and effect of a mutation in the invH gene. Infect. Immun. 63, 2743–2754Google ScholarPubMed
Wood, M., Rosqvist, W. R., Mullan, P. B., Edwards, M. H., and Galyov, E. E. (1996). SopE, a secreted protein of Salmonella dublin, is translocated into the target eukaryotic cell via a sip-dependent mechanism and promotes bacterial entry. Mol. Microbiol. 22, 327–338CrossRefGoogle Scholar
Zhang, S., Santos, R. L., Tsolis, R. M., Stender, S., Hardt, W. D., Baumler, A. J., and Adams, L. G. (2002). The Salmonella enterica Serotype Typhimurium effector proteins SiPA, SoPA, SopB, SopD, and SopE2 act in concert to induce diarrhea in calves. Infect. Immun. 70, 3843–3855CrossRefGoogle ScholarPubMed
Zhou, D. and Galan, J. E. (2001). Salmonella entry into host cells: the work in concert of type III secreted effector proteins. Microb. Infect. 3, 1293–1298CrossRefGoogle ScholarPubMed
Zhou, D., Chen, L. L. H., Shears, B. S., and Galan, J. E. (2001). A Salmonella inositol polyphosphatase acts in conjunction with other bacterial effectors to promote host-cell actin cytoskeleton rearrangements and bacterial internalization. Mol. Microbiol. 39, 248–259CrossRefGoogle ScholarPubMed
Zhou, D., Mooseker, M. S., and Galan, J. E. (1999a). An invasion-associated Salmonella protein modulates the actin-bundling activity of plastin. Proc. Natl. Acad. Sci. USA 96, 10,176–10,181CrossRefGoogle Scholar
Zhou, D., Mooseker, M. S., and Galan, J. E. (1999b). Role of S. typhimurium actin-binding protein SipA in bacterial internalization. Science 283, 2092–2095CrossRefGoogle Scholar

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  • Invasion mechanisms of Salmonella
    • By Beth A. McCormick, Department of Pediatric Gastroenterology and Nutrition, Mucosal Immunology Laboratory, Massachusetts General Hospital, Charlestown, Massachusetts 02129-4404, USA
  • Edited by Richard J. Lamont, University of Florida
  • Book: Bacterial Invasion of Host Cells
  • Online publication: 21 August 2009
  • Chapter DOI: https://doi.org/10.1017/CBO9780511546273.003
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  • Invasion mechanisms of Salmonella
    • By Beth A. McCormick, Department of Pediatric Gastroenterology and Nutrition, Mucosal Immunology Laboratory, Massachusetts General Hospital, Charlestown, Massachusetts 02129-4404, USA
  • Edited by Richard J. Lamont, University of Florida
  • Book: Bacterial Invasion of Host Cells
  • Online publication: 21 August 2009
  • Chapter DOI: https://doi.org/10.1017/CBO9780511546273.003
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  • Invasion mechanisms of Salmonella
    • By Beth A. McCormick, Department of Pediatric Gastroenterology and Nutrition, Mucosal Immunology Laboratory, Massachusetts General Hospital, Charlestown, Massachusetts 02129-4404, USA
  • Edited by Richard J. Lamont, University of Florida
  • Book: Bacterial Invasion of Host Cells
  • Online publication: 21 August 2009
  • Chapter DOI: https://doi.org/10.1017/CBO9780511546273.003
Available formats
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