Bacterial Adherence, Colonization, and Invasion of Mucosal Surfaces

John H. Brumell; B. Brett Finlay

doi:10.1128/9781555818111.ch1

Chapter 1 : Bacterial Adherence, Colonization, and Invasion of Mucosal Surfaces

Authors: John H. Brumell¹, B. Brett Finlay¹

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Affiliations: 1: Biotechnology Laboratory, University of British Columbia, Room 237-Wesbrook Building, 6174 University Boulevard, Vancouver, British Columbia, Canada V6T 1Z3

Content Type: Monograph

Publication Year: 2000

Category: Bacterial Pathogenesis

Book DOI: 10.1128/9781555818111

Chapter DOI: 10.1128/9781555818111.ch1

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Abstract:

This chapter provides a brief overview of the pathogenic strategies of some bacteria that infect the mucosal surface of the intestinal tract. It focuses on two model systems for the study of bacterial pathogens that cause disease by colonizing (enteropathogenic Escherichia coli [EPEC]) or penetrating (Salmonella species) the intestinal epithelium. Mucosal surfaces have many physiological defenses against pathogenic bacteria. These include entrapment in a thick blanket of mucus and clearance by peristalsis in the gut or ciliary movement in the airways. Adhesins on the bacterial surface provide specificity for interaction with target host cells. For example, M cells of the intestinal epithelium have cell surface glycosylation patterns that vary between species and tissue location. Adhesion is often a prerequisite for penetration of the mucosal surface, though different pathogens penetrate this barrier by different means and with different ends. EPEC provides a suitable model for understanding A/E pathogens and has largely been studied in vitro by infection of epithelial tissue cell cultures. Salmonella species infect a broad range of animals and can cause different diseases in different hosts. For example Salmonella enterica serovar Typhi causes typhoid fever in humans, which can be fatal. Recent progress has revealed the mechanisms by which the translocated effectors of SPI-1 mediate invasion by Salmonella serovar Typhimurium. Pathogenic bacteria have evolved different strategies to initiate infection at mucosal surfaces.

Citation: Brumell J, Finlay B. 2000. Bacterial Adherence, Colonization, and Invasion of Mucosal Surfaces, p 3-17. In Brogden K, Roth J, Stanton T, Bolin C, Minion F, Wannemuehler M (ed), Virulence Mechanisms of Bacterial Pathogens, Third Edition. ASM Press, Washington, DC. doi: 10.1128/9781555818111.ch1

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Bacterial Adherence, Colonization, and Invasion of Mucosal Surfaces

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FIGURE 1

Type III secretion systems of EPEC and Salmonella serovar Typhimurium. Depicted are the needle-like complexes ( 44 ) that span both bacterial membranes of the pathogen and deliver translocated effector proteins into the host cell. These effector proteins can then manipulate host signaling systems. Note that Salmonella serovar Typhimurium express two type III secretion systems: one that delivers effectors across the plasma membrane (encoded within SPI-1) to mediate invasion (see text), and a separate system that mediates survival and replication within host cells (SPI-2) by delivering effector proteins across the membrane of the SCV. Artwork provided by A. Gauthier.

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FIGURE 1

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FIGURE 2

Models of EPEC pathogenesis. (A) Formation of pedestals by EPEC on the surface of HeLa epithelial cells in vitro. Scanning electron micrograph provided by Dr. I. Rosenshine. (B) Formation of A/E lesions in vivo by REPEC 0103. Pedestal formation on the intestinal surface is indicated with arrows. Note that on these cells, effacement of microvilli has occurred (compare to upper right hand side). TEM provided by Dr. U. Heczko and reproduced from The Journal of Experimental Medicine, 1998, volume 188, pages 1907–1916 ( 1 ) by copyright permission of the Rockefeller University Press. (C) Three-stage model of EPEC pedestal formation. In the first step, attachment of EPEC is mediated by bundle-forming pilus (BFP) binding to the epithelial cell surface. Next, the type III secretion system mediates delivery of both Esp's and the Tir. Intiminindependent host signals are activated and Tir is phosphorylated by an unknown tyrosine kinase. Finally, intimin binding mediates clustering of phosphorylated Tir, intimin-dependent host signals are activated, and rearrangements of the host actin cytoskeleton cause pedestal formation. Artwork provided by Dr. R. DeVinney and reprinted from Current Opinion in Microbiology, volume 2, pages 83–88, copyright 1999 ( 14 ), with permission from Elsevier Science.

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FIGURE 2

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FIGURE 3

Models of Salmonella serovar Typhimurium pathogenesis. (A) Cell-surface ruffling of Caco-2 epithelial cells induced by Salmonella serovar Typhimurium. Note the loss of microvilli near bacteria and the formation of large ruffles. (B) Uptake of Salmonella serovar Typhimurium in large vacuoles that resemble macropinosomes in vitro. (C) Invasion of epithelial cells by delivery of translocated effectors into the host cell. Depicted are the translocated effectors of the SPI-1-encoded type III secretion system and the host signaling systems that they directly interact with. These effectors have numerous effects on the host cell, including ruffling of the cell surface (thereby directing Salmonella serovar Typhimurium uptake), production of proinflammatory cytokines, and apoptosis. Artwork modified from Current Biology ( 6 ) with permission from Elsevier Science. (D) Intracellular trafficking of Salmonella serovar Typhimurium in host cells. Upon entry into host cells, serovar Typhimurium remain in a vacuolar compartment (SCV) that interacts transiently with early endosomes. However, these vacuoles do not undergo further processing within the endosomal system and do not fuse with mature lysosomes. Instead, the SCV appear to interact with an unknown compartment that mediates delivery of lysosomal glycoproteins (such as LAMP-1) but not degradative lysosomal enzymes such as cathepsin D ( 48 ). After several hours, intracellular Salmonella serovar Typhimurium begins to replicate and long, contiguous tubules (Sifs) are formed. Artwork provided by O. Steele-Mortimer and modified from Cellular Microbiology ( 65 ) with permission from Blackwell Science Ltd.

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References

/content/book/10.1128/9781555818111.chap1

1. Abe, A.,, U. Heczko,, R. G. Hegele,, and B. B. Finlay. 1998. Two enteropathogenic Escherichia coli type III secreted proteins, EspA and EspB, are virulence factors. J. Exp. Med. 188: 1907– 1916.

2. Baldwin, T. J.,, W. Ward,, A. Aitken,, S. Knutton,, and P. H. Williams. 1991. Elevation of intracellular free calcium levels in HEp-2 cells infected with enteropathogenic Escherichia coli. Infect. Immun. 59: 1599– 1604.

3. Baumler, A. J.,, R. M. Tsolis,, and F. Heffron. 1996. The lpf fimbrial operon mediates adhesion of Salmonella typhimurium to murine Peyer’s patches. Proc. Natl. Acad. Sci. USA 93: 279– 283.

4. Bieber, D.,, S. W. Ramer,, C. Y. Wu,, W. J. Murray,, T. Tobe,, R. Fernandez,, and G. K. Schoolnik. 1998. Type IV pili, transient bacterial aggregates, and virulence of enteropathogenic Escherichia coli [see comments]. Science 280: 2114– 2118.

5. Bowe, F.,, C. J. Lipps,, R. M. Tsolis,, E. Groisman,, F. Heffron,, and J. G. Kusters. 1998. At least four percent of the Salmonella typhimurium genome is required for fatal infection of mice. Infect. Immun. 66: 3372– 3377.

6. Brumell, J. H.,, O. Steele-Mortimer,, and B. B. Finlay. 1999. Bacterial invasion: force feeding by Salmonella. Curr. Biol. 9: R277– R280.

7. Buchmeier, N. A.,, C. J. Lipps,, M. Y. So,, and F. Heffron. 1993. Recombinationdeficient mutants of Salmonella typhimurium are avirulent and sensitive to the oxidative burst of macrophages. Mol. Microbiol. 7: 933– 936.

8. Canil, C.,, I. Rosenshine,, S. Ruschkowski,, M. S. Donnenberg,, J. B. Kaper,, and B. B. Finlay. 1993. Enteropathogenic Escherichia coli decreases the transepithelial electrical resistance of polarized epithelial monolayers. Infect. Immun. 61: 2755– 2762.

9. Cirillo, D. M.,, R. H. Valdivia,, D. M. Monack,, and S. Falkow. 1998. Macrophagedependent induction of the Salmonella pathogenicity island 2 type III secretion system and its role in intracellular survival. Mol. Microbiol. 30: 175– 188.

10. Collazo, C. M.,, and J. E. Galan. 1997. The invasion-associated type-III protein secretion system in Salmonella—a review. Gene 192: 51– 59.

11. Cornelis, G. R. 1998. The Yersinia Yop virulon, a bacterial system to subvert cells of the primary host defense. Folia Microbiol. 43: 253– 261.

12. Crane, J. K.,, and J. S. Oh. 1997. Activation of host cell protein kinase C by enteropathogenic Escherichia coli. Infect. Immun. 65: 3277– 3285.

13. De Rycke, J.,, E. Comtet,, C. Chalareng,, M. Boury,, C. Tasca,, and A. Milon. 1997. Enteropathogenic Escherichia coli O103 from rabbit elicits actin stress fibers and focal adhesions in HeLa epithelial cells, cytopathic effects that are linked to an analog of the locus of enterocyte effacement. Infect. Immun. 65: 2555– 2563.

14. DeVinney, R.,, D. G. Knoechel,, and B. B. Finlay. 1999. Enteropathogenic Escherichia coli: cellular harassment. Curr. Opin. Microbiol. 2: 83– 88.

15. DeVinney, R.,, M. Stein,, D. Reinscheid,, A. Abe,, S. Ruschkowski,, and B. B. Finlay. 1999. Enterohemorrhagic Escherichia coli O157: H7 produces Tir, which is translocated to the host cell membrane but is not tyrosine phosphorylated. Infect. Immun. 67: 2389– 2398.

16. Ebel, F.,, T. Podzadel,, M. Rohde,, A. U. Kresse,, S. Kramer,, C. Deibel,, C. A. Guzman,, and T. Chakraborty. 1998. Initial binding of Shiga toxin-producing Escherichia coli to host cells and subsequent induction of actin rearrangements depend on filamentous EspAcontaining surface appendages. Mol. Microbiol. 30: 147– 161.

17. Elliott, S. J.,, L. A. Wainwright,, T. K. McDaniel,, K. G. Jarvis,, Y. K. Deng,, L. C. Lai,, B. P. McNamara,, M. S. Donnenberg,, and J. B. Kaper. 1998. The complete sequence of the locus of enterocyte effacement (LEE) from enteropathogenic Escherichia coli E2348/69. Mol. Microbiol. 28: 1– 4.

18. Fang, F. C.,, M. A. DeGroote,, J. W. Foster,, A. J. Baumler,, U. Ochsner,, T. Testerman,, S. Bearson,, J. C. Giard,, Y. Xu,, G. Campbell,, and T. Laessig. 1999. Virulent Salmonella typhimurium has two periplasmic Cu, Znsuperoxide dismutases. Proc. Natl. Acad. Sci. USA 96: 7502– 7507.

19. Fields, P. I.,, R. V. Swanson,, C. G. Haidaris,, and F. Heffron. 1986. Mutants of Salmonella typhimurium that cannot survive within the macrophage are avirulent. Proc. Natl. Acad. Sci. USA 83: 5189– 5193.

20. Foubister, V.,, I. Rosenshine,, and B. B. Finlay. 1994. A diarrheal pathogen, enteropathogenic Escherichia coli (EPEC), triggers a flux of inositol phosphates in infected epithelial cells. J. Exp. Med. 179: 993– 998.

21. Frankel, G.,, A. D. Phillips,, I. Rosenshine,, G. Dougan,, J. B. Kaper,, and S. Knutton. 1998. Enteropathogenic and enterohaemorrhagic Escherichia coli: more subversive elements. Mol. Microbiol. 30: 911– 921.

22. Fu, Y.,, and J. E. Galan. 1998. The Salmonella typhimurium tyrosine phosphatase SptP is translocated into host cells and disrupts the actin cytoskeleton. Mol. Microbiol. 27: 359– 368.

23. Galan, J. E.,, and R. D. Curtiss. 1989. Cloning and molecular characterization of genes whose products allow Salmonella typhimurium to penetrate tissue culture cells. Proc. Natl. Acad. Sci. USA 86: 6383– 6387.

24. Garcia-del Portillo, F.,, and B. B. Finlay. 1994. Salmonella invasion of nonphagocytic cells induces formation of macropinosomes in the host cell. Infect. Immun. 62: 4641– 4645.

25. Garcia-del Portillo, F.,, and B. B. Finlay. 1995. Targeting of Salmonella typhimurium to vesicles containing lysosomal membrane glycoproteins bypasses compartments with mannose 6- phosphate receptors. J. Cell Biol. 129: 81– 97.

26. Goosney, D. L.,, J. Celli,, B. Kenny,, and B. B. Finlay. 1999. Enteropathogenic Escherichia coli inhibits phagocytosis. Infect. Immun. 67: 490– 495.

27. Goosney, D. L.,, M. de Grado,, and B. B. Finlay. 1999. Putting E. coli on a pedestal: a unique system to study signal transduction and the actin cytoskeleton. Trends Cell Biol. 9: 11– 14.

28. Groisman, E. A.,, and H. Ochman. 1997. How Salmonella became a pathogen. Trends Microbiol. 5: 343– 349.

29. Hardt, W. D.,, L. M. Chen,, K. E. Schuebel,, X. R. Bustelo,, and J. E. Galan. 1998. S. typhimurium encodes an activator of Rho GTPases that induces membrane ruffling and nuclear responses in host cells. Cell 93: 815– 826.

30. Hardt, W. D.,, H. Urlaub,, and J. E. Galan. 1998. A substrate of the centisome 63 type III protein secretion system of Salmonella typhimurium is encoded by a cryptic bacteriophage. Proc. Natl. Acad. Sci. USA 95: 2574– 2579.

31. Hein, W. R., 1999. Organization of mucosal lymphoid tissue, p. 1– 15. In J.-P. Kraehenbuhl, and M. R. Neutra (ed.), Defences of Mucosal Surfaces: Pathogenesis, Immunity and Vaccines. Springer-Verlag, Heidelberg, Germany.

32. Hensel, M.,, J. E. Shea,, S. R. Waterman,, R. Mundy,, T. Nikolaus,, G. Banks,, A. Vazquez- Torres,, C. Gleeson,, F. C. Fang,, and D. W. Holden. 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– 174.

33. Hersh, D.,, D. M. Monack,, M. R. Smith,, N. Ghori,, S. Falkow,, and A. Zychlinsky. 1999. The Salmonella invasin SipB induces macrophage apoptosis by binding to caspase-1. Proc. Natl. Acad. Sci. USA 96: 2396– 2401.

34. Hoiseth, S. K.,, and B. A. Stocker. 1981. Aromatic-dependent Salmonella typhimurium are non-virulent and effective as live vaccines. Nature 291: 238– 239.

35. Hong, K. H.,, and V. L. Miller. 1998. Identification of a novel Salmonella invasion locus homologous to Shigella ipgDE. J. Bacteriol. 180: 1793– 1802.

36. Hueck, C. J. 1998. Type III protein secretion systems in bacterial pathogens of animals and plants. Microbiol. Mol. Biol. Rev. 62: 379– 433.

37. Jones, B. D.,, and S. Falkow. 1996. Salmonellosis: host immune responses and bacterial virulence determinants. Annu. Rev. Immunol. 14: 533– 561.

38. Kaper, J. B.,, J. G. Morris, Jr.,, and M. M. Levine. 1995. Cholera. Clin. Microbiol. Rev. 8: 48– 86. [ Erratum, Clin. Microbiol. Rev. 8:316.]

39. Kenny, B. 1999. Phosphorylation of tyrosine 474 of the enteropathogenic Escherichia coli (EPEC) Tir receptor molecule is essential for actin nucleating activity and is preceded by additional host modifications. Mol. Microbiol. 31: 1229– 1241.

40. Kenny, B.,, R. DeVinney,, M. Stein,, D. J. Reinscheid,, E. A. Frey,, and B. B. Finlay. 1997. Enteropathogenic E. coli (EPEC) transfers its receptor for intimate adherence into mammalian cells. Cell 91: 511– 520.

41. Kenny, B.,, and B. B. Finlay. 1997. Intimindependent binding of enteropathogenic Escherichia coli to host cells triggers novel signaling events, including tyrosine phosphorylation of phospholipase C-gamma1. Infect. Immun. 65: 2528– 2536.

42. Kim, J. M.,, L. Eckmann,, T. C. Savidge,, D. C. Lowe,, T. Witthoft,, and M. F. Kagnoff. 1998. Apoptosis of human intestinal epithelial cells after bacterial invasion. J. Clin. Invest. 102: 1815– 1823.

43. Knutton, S.,, I. Rosenshine,, M. J. Pallen,, I. Nisan,, B. C. Neves,, C. Bain,, C. Wolff,, G. Dougan,, and G. Frankel. 1998. A novel EspAassociated surface organelle of enteropathogenic Escherichia coli involved in protein translocation into epithelial cells. EMBO J. 17: 2166– 2176.

44. Kubori, T.,, Y. Matsushima,, D. Nakamura,, J. Uralil,, M. Lara-Tejero,, A. Sukhan,, J. E. Galan,, and S. I. Aizawa. 1998. Supramolecular structure of the Salmonella typhimurium type III protein secretion system. Science 280: 602– 605.

45. Lundberg, B. E.,, R. E. Wolf, Jr.,, M. C. Dinauer,, Y. Xu,, and F. C. Fang. 1999. Glucose 6-phosphate dehydrogenase is required for Salmonella typhimurium virulence and resistance to reactive oxygen and nitrogen intermediates. Infect. Immun. 67: 436– 438.

46. Manjarrez-Hernandez, H. A.,, B. Amess,, L. Sellers,, T. J. Baldwin,, S. Knutton,, P. H. Williams,, and A. Aitken. 1991. Purification of a 20 kDa phosphoprotein from epithelial cells and identification as a myosin light chain. Phosphorylation induced by enteropathogenic Escherichia coli and phorbol ester. FEBS Lett. 292: 121– 127.

47. McNamara, B. P.,, and M. S. Donnenberg. 1998. A novel proline-rich protein, EspF, is secreted from enteropathogenic Escherichia coli via the type III export pathway. FEMS Microbiol. Lett. 166: 71– 78.

48. Méresse, S.,, O. Steele-Mortimer,, B. B. Finlay,, and J. P. Gorvel. 1999. The rab7 GTPase controls the maturation of Salmonella typhimurium- containing vacuoles in HeLa cells. EMBO J. 18: 4394– 4403.

49. Mills, S. D.,, and B. B. Finlay. 1998. Isolation and characterization of Salmonella typhimurium and Yersinia pseudotuberculosis-containing phagosomes from infected mouse macrophages: Y. pseudotuberculosis traffics to terminal lysosomes where they are degraded. Eur. J. Cell Biol. 77: 35– 47.

50. Monack, D. M.,, B. Raupach,, A. E. Hromockyj,, and S. Falkow. 1996. Salmonella typhimurium invasion induces apoptosis in infected macrophages. Proc. Natl. Acad. Sci. USA 93: 9833– 9838.

51. Neutra, M. R., 1999. M cells in antigen sampling in mucosal tissues, p. 17– 32. In J.-P. Kraehenbuhl, and M. R. Neutra (ed.), Defences of Mucosal Surfaces: Pathogenesis, Immunity and Vaccines, 1st ed. Springer-Verlag, New York, N.Y.

52. Norris, F. A.,, M. P. Wilson,, T. S. Wallis,, E. E. Galyov,, and P. W. Majerus. 1998. SopB, a protein required for virulence of Salmonella dublin, is an inositol phosphate phosphatase [see comments]. Proc. Natl. Acad. Sci. USA 95: 14057– 14059.

53. Ochman, H.,, F. C. Soncini,, F. Solomon,, and E. A. Groisman. 1996. Identification of a pathogenicity island required for Salmonella survival in host cells. Proc. Natl. Acad. Sci. USA 93: 7800– 7804.

54. Pier, G. B.,, M. Grout,, T. Zaidi,, G. Meluleni,, S. S. Mueschenborn,, G. Banting,, R. Ratcliff,, M. J. Evans,, and W. H. Colledge. 1998. Salmonella typhi uses CFTR to enter intestinal epithelial cells. Nature 393: 79– 82.

55. Rathman, M.,, L. P. Barker,, and S. Falkow. 1997. The unique trafficking pattern of Salmonella typhimurium-containing phagosomes in murine macrophages is independent of the mechanism of bacterial entry. Infect. Immun. 65: 1475– 1485.

56. Raupach, B.,, J. Mecsas,, U. Heczko,, S. Falkow,, and B. B. Finlay. 1999. Bacterial epithelial cell cross talk. Curr. Top. Microbiol. Immunol. 236: 137– 161.

57. Richter-Dahlfors, A.,, A. M. J. Buchan,, and B. B. Finlay. 1997. Murine salmonellosis studied by confocal microscopy: Salmonella typhimurium resides intracellularly inside macrophages and exerts a cytotoxic effect on phagocytes in vivo. J. Exp. Med. 186: 569– 580.

58. Rosenshine, I.,, S. Ruschkowski,, M. Stein,, D. J. Reinscheid,, S. D. Mills,, and B. B. Finlay. 1996. A pathogenic bacterium triggers epithelial signals to form a functional bacterial receptor that mediates actin pseudopod formation. EMBO J. 15: 2613– 2624.

59. Ruckdeschel, K.,, A. Roggenkamp,, V. Lafont,, P. Mangeat,, J. Heesemann,, and B. Rouot. 1997. Interaction of Yersinia enterocolitica with macrophages leads to macrophage cell death through apoptosis. Infect. Immun. 65: 4813– 4821.

60. Salama, N. R.,, and S. Falkow. 1999. Genomic clues for defining bacterial pathogenicity. Microb. Infect. 1: 615– 619.

61. Salyers, A. A.,, and D. D. Whitt. 1994. Bacterial Pathogenesis: A Molecular Approach. ASM Press, Washington, D.C.

62. Sansonetti, P. J.,, G. Tran Van Nhieu,, and C. Egile. 1999. Rupture of the intestinal epithelial barrier and mucosal invasion by Shigella flexneri. Clin. Infect. Dis. 28: 466– 475.

63. Shea, J. E.,, M. Hensel,, C. Gleeson,, and D. W. Holden. 1996. Identification of a virulence locus encoding a second type III secretion system in Salmonella typhimurium. Proc. Natl. Acad. Sci. USA 93: 2593– 2597.

64. Siebers, A.,, and B. B. Finlay. 1996. M cells and the pathogenesis of mucosal and systemic infections. Trends Microbiol. 4: 22– 29.

65. Steele-Mortimer, O.,, S. Méresse,, J.-P. Gorvel,, B.-H. Toh,, and B. B. Finlay. 1999. Biogenesis of Salmonella typhimurium-containing vacuoles in epithelial cells involves interactions with the early endocytic pathway. Cell. Microbiol. 1: 33– 51.

66. Uchiya, K.,, M. A. Barbieri,, K. Funato,, A. H. Shah,, P. D. Stahl,, and E. A. Groisman. 1999. A salmonella virulence protein that inhibits cellular trafficking. EMBO J. 18: 3924– 3933.

67. Wachter, C.,, C. Beinke,, M. Mattes,, and M. A. Schmidt. 1999. Insertion of EspD into epithelial target cell membranes by infecting enteropathogenic Escherichia coli. Mol. Microbiol. 31: 1695– 1707.

68. Wolff, C.,, I. Nisan,, E. Hanski,, G. Frankel,, and I. Rosenshine. 1998. Protein translocation into host epithelial cells by infecting enteropathogenic Escherichia coli. Mol. Microbiol. 28: 143– 155.

69. Wood, M. W.,, M. A. Jones,, P. R. Watson,, S. Hedges,, T. S. Wallis,, and E. E. Galyov. 1998. Identification of a pathogenicity island required for Salmonella enteropathogenicity. Mol.Microbiol. 29: 883– 891.

70. Zhou, D.,, M. S. Mooseker,, and J. E. Galan. 1999. Role of the S. typhimurium actin-binding protein SipA in bacterial internalization. Science 283: 2092– 2095.

71. Zychlinsky, A.,, M. C. Prevost,, and P. J. Sansonetti. 1992. Shigella flexneri induces apoptosis in infected macrophages. Nature 358: 167– 169.