Exploitation of Mammalian Host Cell Function by Shigella spp.

Larean D. Brandon; Marcia B. Goldberg

doi:10.1128/9781555818111.ch12

Chapter 12 : Exploitation of Mammalian Host Cell Function by Shigella spp.

Authors: Larean D. Brandon¹, Marcia B. Goldberg¹

VIEW AFFILIATIONS HIDE AFFILIATIONS

Affiliations: 1: Infectious Disease Division, Massachusetts General Hospital, 55 Fruit St., Boston, MA 02114

Content Type: Monograph

Publication Year: 2000

Category: Bacterial Pathogenesis

Book DOI: 10.1128/9781555818111

Chapter DOI: 10.1128/9781555818111.ch12

MyBook is a cheap paperback edition of the original book and will be sold at uniform, low price.

Preview this chapter:

Exploitation of Mammalian Host Cell Function by Shigella spp., Page 1 of 2

< Previous page | Next page > /docserver/preview/fulltext/10.1128/9781555818111/9781555811747_Chap12-1.gif /docserver/preview/fulltext/10.1128/9781555818111/9781555811747_Chap12-2.gif

Abstract:

Shigella species are the causative agents of shigellosis (a form of bacillary dysentery) and lead to an estimated 1.1 million deaths per annum, most notably in developing world countries where nutrition and hygiene are suboptimal. The pathogenicity of Shigella depends upon a complex series of molecular events that are mediated by factors expressed on the large 220-kilobase virulence plasmid. This chapter describes the detailed molecular events involved in these interactions of shigellae with the host cell. Shigellae invade human colonic epithelial cells. The initial step in the pathogenesis of shigellosis most likely involves specific interactions of the organism, with the mucin associated with the apical surface of colonic epithelial cells. In vitro studies demonstrate that shigellae are unable to enter polarized colonic epithelial cells at the apical pole, but rather can enter only at the basolateral surfaces. Entry of Shigella at the basolateral face of colonic epithelial cells involves a complex set of molecular reactions. The SSRRASS phosphorylation consensus sequence in IcsA contains the site for processing by the IcsP (SopA) outer membrane protease. Genetic and biochemical studies demonstrate that IcsA is an autotransported protein and therefore can be included in the family of proteins that use the Type IV secretion pathway. VirF (a protein expressed on the virulence plasmid) is the global regulator of the virulence genes on the large 220-kb plasmid. Most of the genes known to be regulated by VirF have been discussed in the chapter.

Citation: Brandon L, Goldberg M. 2000. Exploitation of Mammalian Host Cell Function by Shigella spp., p 175-187. 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.ch12

Key Concept Ranking

Bacterial Proteins: 0.739647
Bacterial Diseases: 0.57415885
Outer Membrane Proteins: 0.46170688
Bacterial Virulence Factors: 0.4425484

0.739647

Highlighted Text: Show | Hide

Full text loading...

Figures

Exploitation of Mammalian Host Cell Function by Shigella spp.

[com.pub2web.rdf.cci.facet.ContentItem[id=http://asm.metastore.ingenta.com/content/author/10.1128/9781555818111.chap12-1,webId=/content/author/10.1128/9781555818111.chap12-1,properties={foaf_givenname=Larean D., foaf_name=Larean D. Brandon, foaf_surname=Brandon, pub_isAffiliatedWith=[com.pub2web.rdf.cci.facet.ContentItem[id=http://asm.metastore.ingenta.com/content/affiliation/10.1128/9781555818111.chap12-aff1]]}], com.pub2web.rdf.cci.facet.ContentItem[id=http://asm.metastore.ingenta.com/content/author/10.1128/9781555818111.chap12-2,webId=/content/author/10.1128/9781555818111.chap12-2,properties={foaf_givenname=Marcia B., foaf_name=Marcia B. Goldberg, foaf_surname=Goldberg, pub_isAffiliatedWith=[com.pub2web.rdf.cci.facet.ContentItem[id=http://asm.metastore.ingenta.com/content/affiliation/10.1128/9781555818111.chap12-aff1]]}]]

/content/10.1128/9781555818111.chap12.fig12-1

FIGURE 1

Simplified schematic of the pathogenesis of shigellosis. Shigellae (black ovals) are initially taken up by M cells (cell A) and transcytosed to the basolateral face of the epithelial cells, where they are engulfed by macrophages (cell B). The bacteria release factors that promote apoptosis of the macrophages (thereby releasing the bacteria) and that promote the release of interleukin 1-β. This release promotes an inflammatory response that induces the transmigration of PMNs (cell C) between the epithelial cells to the apical face of the epithelial cell layer. The inflammatory response destroys the integrity of the tight junctions (black rectangles), thus enhancing uptake of the bacteria. Once the bacteria reach the basolateral face of the epithelial cells they are endocytosed and rapidly escape the endocytic vesicle (steps 1 and 2). They are subsequently released into the host cell cytoplasm where they divide ( 3 ), recruit actin filaments ( 4 ), and invade adjacent epithelial cells via actin-mediated motility ( 5 ). In the new host cell, the bacteria are found associated with double-membrane vesicles, from which they rapidly escape ( 6 and 7 ).

10.1128/9781555818111/fig12-1_thmb.gif

10.1128/9781555818111/fig12-1.gif

FIGURE 1

/content/10.1128/9781555818111.chap12.fig12-2

FIGURE 2

Proposed mechanism of targeting of IcsA to the bacterial old pole. Following translation, the targeting domain of IcsA (star) recognizes a polar target (hexagon) associated with the cytoplasmic membrane at the old pole. IcsA is then translocated across the cytoplasmic membrane at the pole and its carboxyterminal β domain is inserted into the outer membrane, such that the aminoterminal α domain is exposed on the bacterial surface. Following insertion into the outer membrane, IcsA diffuses laterally in the membrane. IcsP cleaves IcsA from all surfaces of the bacteria at a rate that is slower than the rate at which IcsA is inserted at the pole, such that a polar cap of IcsA is maintained.

10.1128/9781555818111/fig12-2_thmb.gif

10.1128/9781555818111/fig12-2.gif

FIGURE 2

/content/10.1128/9781555818111.chap12.fig12-3

FIGURE 3

Model of IcsA-mediated actin assembly. The amino-terminal glycine-rich repeat domain of IcsA (shaded bar) binds the verprolin (V) domain of N-WASP (open bar). This binding leads to unmasking of carboxy- terminal domains of N-WASP, thereby allowing binding of the Arp2/ 3 complex to the N-WASP acidic domain (A) and G-actin (Ag) to the N-WASP verprolin (V) domain. In the presence of the Arp2/3 complex actin is nucleated, with the Arp2/3 complex capping the pointed end of the actin nucleus. G-actin (Ag) is rapidly polymerized onto the uncapped barbed end. Subsequently, N-WASP and the growing actin filament are released from IcsA and crosslinked into the actin tail. Af, filamentous actin.

10.1128/9781555818111/fig12-3_thmb.gif

10.1128/9781555818111/fig12-3.gif

FIGURE 3

/content/10.1128/9781555818111.chap12.fig12-4

FIGURE 4

Model for modulating the expression of virulence genes. VirF is the global regulator of genes found on the virulence plasmid. The chromosomally encoded CpxA/CpxR two-component regulatory proteins regulate VirF. VirF activates the transcription of icsA and virB. The latter's gene product activates the transcription of the mxi-spa locus and the ipa operon. The chromosomally encoded H-NS protein is an antagonistic regulatory factor that represses the expression of virB at 30°C, but which is released from the virB promoter at 37°C.

10.1128/9781555818111/fig12-4_thmb.gif

10.1128/9781555818111/fig12-4.gif

FIGURE 4

References

/content/book/10.1128/9781555818111.chap12

1. Adam, T.,, M. Arpin,, M. C. Prevost,, P. Gounon,, and P. J. Sansonetti. 1995. Cytoskeletal rearrangements and the functional role of T-plastin during entry of Shigella flexneri into HeLa cells. J. Cell. Biol. 129: 367– 381.

2. Adam, T.,, M. Giry,, P. Boquet,, and P. J. Sansonetti. 1996. Rho-dependent membrane folding causes Shigella entry into epithelial cells. EMBO J. 15: 3315– 3321.

3. Adler, B.,, C. Sasakawa,, T. Tobe,, S. Makino,, K. Komatsu,, and M. Yoshikawa. 1989. A dual transcriptional activation system for the 230 kb plasmid genes coding for virulence associated antigens of Shigella flexneri. Mol. Microbiol. 3: 627– 635.

4. Allaoui, A.,, J. Mounier,, M.-C. Prevost,, P. J. Sansonetti,, and C. Parsot. 1992. icsB: a Shigella flexneri virulence gene necessary for the lysis of protrusions during intercellular spread. Mol. Microbiol. 6: 1605– 1616.

5. Bahrani, F. K.,, P. J. Sansonetti,, and C. Parsot. 1997. Secretion of Ipa proteins by Shigella flexneri : inducer molecules and kinetics of activation. Infect. Immun. 65: 4005– 4010.

6. Bernardini, M. L.,, A. Fontaine,, and P. J. Sansonetti. 1990. The two-component regulatory system OmpR-EnvZ controls the virulence of Shigella flexneri. J. Bacteriol. 172: 6274– 6281.

7. Bernardini, M. L.,, J. Mounier,, H. d’Hauteville,, M. Coquis-Rondon,, and P. J. Sansonetti. 1989. Identification of icsA, a plasmid locus of Shigella flexneri that governs bacterial intra- and intercellular spread through interaction with F-actin. Proc. Natl. Acad. Sci. USA 86: 3867– 3871.

8. Chen, Y.,, M. Smith,, K. Thirumalai,, and A. Zychlinsky. 1996. A bacterial invasin induces macrophage apoptosis by binding directly to ICE. EMBO J. 15: 3853– 3860.

9. Clerc, P.,, and P. J. Sansonetti. 1987. Entry of Shigella flexneri into HeLa cells: evidence for directed phagocytosis involving actin polymerization and myosin accumulation. Infect. Immun. 55: 2681– 2688.

10. Cornelis, G. R.,, and H. Wolf-Watz. 1997. The Yersinia Yop virulon: a bacterial system for subverting eukaryotic cells. Mol. Microbiol. 23: 861– 867.

11. DeGeyter, C.,, B. Vogt,, Z. Benjelloun- Touimi,, P. J. Sansonetti,, J.-M. Ruysschaert,, C. Parsot,, and V. Cabiaux. 1997. Purification of IpaC, a protein involved in entry of Shigella flexneri into epithelial cells and characterization of its interaction with lipid membranes. FEBS Lett. 400: 149– 154.

12. Dehio, C.,, M. C. Prevost,, and P. J. Sansonetti. 1995. Invasion of epithelial cells by Shigella flexneri induces phosphorylation of cortactin by a pp60c-src-mediated signalling pathway. EMBO J. 14: 2471– 2482.

13. d’Hauteville, H.,, R. D. Lagelouse,, F. Nato,, and P. J. Sansonetti. 1996. Lack of cleavage of IcsA in Shigella flexneri causes aberrant movement and allows demonstration of a cross-reactive eukaryotic protein. Infect. Immun. 64: 511– 517.

14. DuPont, H. L., 1995. Shigella species (bacillary dysentery), p. 2033– 2039. In G. L. Mandell,, J. E. Bennett,, and R. Dolin (ed.), Principles and Practice of Infectious Diseases. Churchill Livingstone, New York, N.Y.

15. Egile, C.,, H. d’Hauteville,, C. Parsot,, and P. J. Sansonetti. 1997. SopA, the outer membrane protease responsible for polar localization of IcsA in Shigella flexneri. Mol. Microbiol. 23: 1063– 1073.

16. Finlay, B. B.,, and P. Cossart. 1997. Exploitation of mammalian host cell functions by bacterial pathogens. Science 276: 718– 725.

17. Fukuda, I.,, T. Suzuki,, H. Munakata,, N. Hayashi,, E. Katayama,, M. Yoshizawa,, and C. Sasakawa. 1995. Cleavage of Shigella surface protein VirG occurs at a specific site, but the secretion is not essential for intracellular spreading. J. Bacteriol. 177: 1719– 1726.

18. Goldberg, M. B. 1997. Shigella actin-based motility in the absence of vinculin. Cell Motil. Cytoskeleton 37: 44– 53.

19. Goldberg, M. B.,, O. Barzu,, C. Parsot,, and P. J. Sansonetti. 1993. Unipolar localization and ATPase activity of IcsA, a Shigella flexneri protein involved in intracellular movement. J. Bacteriol. 175: 2189– 2196.

20. Goldberg, M. B.,, and J. A. Theriot. 1995. Shigella flexneri surface protein IcsA is sufficient to direct actin-based motility. Proc. Natl. Acad. Sci. USA 92: 6572– 6576.

21. Goldberg, M. B.,, J. A. Theriot,, and P. J. Sansonetti. 1994. Regulation of surface presentation of IcsA, a Shigella protein essential to intracellular movement and spread, is growth phase-dependent. Infect. Immun. 62: 5664– 5668.

22. Hale, T. L. 1991. Genetic basis of virulence of Shigella species. Microbiol. Rev. 55: 206– 224.

23. Henderson, I. R.,, F. Navarro-Garcia,, and J. P. Nataro. 1998. The great escape: structure and function of the autotransporter proteins. Trends Microbiol. 6: 370– 378.

24. High, N.,, J. Mounier,, M. C. Prevost,, and P. J. Sansonetti. 1992. IpaB of Shigella flexneri causes entry into epithelial cells and escape from the phagocytic vacuole. EMBO J. 11: 1991– 1999.

25. Isberg, R. 1991. Discrimination between intracellular uptake and surface adhesion of bacterial pathogens. Science 252: 934– 938.

26. Jose, J.,, J. Kramer,, T. Klauser,, J. Pohlner,, and T. F. Meyer. 1996. Absence of periplasmic DsbA oxidoreductase facilitates export of cysteine- containing passenger proteins to the Escherichia coli cell surface via the Iga beta autotransporter pathway. Gene 178: 107– 110.

27. Kotloff, K. L.,, J. P. Winickoff,, B. Ivanoff,, J. D. Clemens,, D. L. Swerdlow,, P. J. Sansonetti,, G. K. Adak,, and M. M. Levine. 1999. Global burden of Shigella infections: implications for vaccine development and implementation of control strategies. Bull. W. H. O. 77: 651– 666.

28. Laine, R. O.,, W. Zeile,, F. Kang,, D. L. Purich,, and F. S. Southwick. 1997. Vinculin proteolysis unmasks an ActA homolog for actin-based Shigella motility. J. Cell Biol. 138: 1255– 1264.

29. Majdalani, N.,, and K. Ippen-Ihler. 1996. Membrane insertion of the F-pilin subunit is Sec independent but requires leader peptidase B and the proton motive force. J. Bacteriol. 178: 3742– 3747.

30. Makino, S.,, C. Sasakawa,, K. Kamata,, T. Kurata,, and M. Yoshikawa. 1986. A genetic determinant required for continuous reinfection of adjacent cells on large plasmid in S. flexneri 2a. Cell 46: 551– 555.

31. Marquart, M. E.,, W. L. Picking,, and W. D. Picking. 1996. Soluble invasion plasmid antigen C (IpaC) from Shigella flexneri elicits epithelial cell responses related to pathogen invasion. Infect. Immun. 64: 4182– 4187.

32. Maurelli, A. T.,, B. Baudry,, H. d’Hauteville,, T. L. Hale,, and P. J. Sansonetti. 1985. Cloning of virulence plasmid DNA sequences involved in invasion of HeLa cells by Shigella flexneri. Infect. Immun. 49: 164– 171.

33. Maurelli, A. T.,, and P. J. Sansonetti. 1988. Identification of a chromosomal gene controlling temperature-regulated expression of Shigella flexneri. Proc. Natl. Acad. Sci. USA 85: 2820– 2824.

34. Miki, H.,, T. Sasaki,, Y. Takai,, and T. Takenawa. 1998. Induction of filopodium formation by a WASP-related actin-depolymerizing protein NWASP. Nature 391: 93– 96.

35. 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.

36. Mounier, J.,, V. Laurent,, A. Hall,, P. Fort,, M. F. Carlier,, P. J. Sansonetti,, and C. Egile. 1999. Rho family GTPases control entry of Shigella flexneri into epithelial cells but not intracellular motility. J. Cell. Sci. 112: 2069– 2080.

37. Mounier, J.,, T. Vasselon,, R. Hellio,, M. Lesourd,, and P. Sansonetti. 1992. Shigella flexneri enters human colonic Caco-2 epithelial cells through the basolateral pole. Infect. Immun. 60: 237– 248.

38. Nakayama, S.-I.,, and H. Watanabe. 1995. Involvement of cpxA, a sensor of a twocomponent regulatory system, in the pHdependent regulation of expression of Shigella sonnei virF gene. J. Bacteriol. 177: 5062– 5069.

39. Nakayama, S.-I.,, and H. Watanabe. 1998. Identification of cpxR as a positive regulator essential for the expression of the Shigella sonnei virF gene. J. Bacteriol. 180: 3522– 3528.

40. O’Toole, P. W.,, J. W. Austin,, and T. J. Trust. 1994. Identification and molecular characterization of a major ring-forming surface protein from the gastric pathogen Helicobacter mustelae. Mol. Microbiol. 11: 349– 361.

41. Perdomo, J. J.,, P. Gounon,, and P. J. Sansonetti. 1994. Polymorphonuclear leukocyte transmigration promotes invasion of colonic epithelial monolayer by Shigella flexneri. J. Clin. Invest. 93: 633– 643.

42. Pohlner, J.,, R. Halter,, K. Beyreuther,, and T. F. Meyer. 1987. Gene structure and extracellular secretion of Neisseria gonorrhoeae IgA protease. Nature 325: 458– 462.

43. Prevost, M. C.,, M. Lesourd,, M. Arpin,, F. Vernel,, J. Mounier,, R. Hellio,, and P. J. Sansonetti. 1992. Unipolar reorganization of F-actin layer at bacterial division and bundling of actin filaments by plastin correlate with movement of Shigella flexneri within HeLa cells. Infect. Immun. 60: 4088– 4099.

44. Raivio, T. L.,, and T. J. Silhavy. 1997. Transduction of envelope stress in Escherichia coli by the Cpx two-component system. J. Bacteriol. 179: 7724– 7733.

45. Rajkumar, R.,, H. Devaraj,, and S. Niranjali. 1998. Binding of Shigella to rat and human intestinal mucin. Mol. Cell. Biochem. 178: 261– 268.

46. Rohatgi, R.,, L. Ma,, H. Miki,, M. Lopez,, T. Kirchhausen,, T. Takenawa,, and M. W. Kirschner. 1999. The interaction between NWASP and the Arp2/3 complex links Cdc42-dependent signals to actin assembly. Cell 97: 221– 231.

47. Sandlin, R. C.,, M. B. Goldberg,, and A. T. Maurelli. 1996. Effect of O side chain length and composition on the virulence of Shigella flexneri 2a. Mol. Microbiol. 22: 63– 73.

48. Sandlin, R. C.,, K. A. Lampel,, S. P. Keasler,, M. B. Goldberg,, A. L. Stolzer,, and A. T. Maurelli. 1995. Avirulence of rough mutants of Shigella flexneri : requirement of O antigen for correct unipolar localization of IcsA in bacterial outer membrane. Infect. Immun. 63: 229– 237.

49. Sandlin, R. C.,, and A. T. Maurelli. 1999. Establishment of unipolar localization of IcsA in Shigella flexneri 2a is not dependent on virulence plasmid determinants. Infect. Immun. 67: 350– 356.

50. Sansonetti, P. J. 1998. Pathogenesis of shigellosis: from molecular and cellular biology of epithelial cell invasion to tissue inflammation and vaccine development. Jpn. J. Med. Sci. Biol. 51( Suppl): S69– S80.

51. Sansonetti, P. J.,, J. Arondel,, J.-M. Cavaillon,, and M. Huerre. 1995. Role of interleukin- 1 in the pathogenesis of experimental shigellosis. J. Clin. Invest. 96: 884– 892.

52. Sansonetti, P. J.,, J. Arondel,, M. Huerre,, A. Harada,, and K. Matsushima. 1999. Interleukin- 8 controls bacterial transepithelial translocation at the cost of epithelial destruction in experimental shigellosis. Infect. Immun. 67: 1471– 1480.

53. Sansonetti, P. J.,, D. J. Kopecko,, and S. B. Formal. 1982. Involvement of a plasmid in the invasive ability of Shigella flexneri. Infect. Immun. 35: 852– 860.

54. Sansonetti, P. J.,, J. Mounier,, M. C. Prevost,, and R.-M. Mege. 1994. Cadherin expression is required for the spread of Shigella flexneri between epithelial cells. Cell 76: 829– 839.

55. Shere, K. D.,, S. Sallustio,, A. Manessis,, T. G. D’Aversa,, and M. B. Goldberg. 1997. Disruption of IcsP, the major Shigella protease that cleaves IcsA, accelerates actin-based motility. Mol. Microbiol. 25: 451– 462.

56. Silversmith, R. E.,, and R. B. Bourret. 1999. Throwing the switch in bacterial chemotaxis. Trends Microbiol. 7: 16– 22.

57. Skoudy, A.,, G. Tran Van Nhieu,, N. Mantis,, M. Arpin,, J. Mounier,, P. Gounon,, and P. Sansonetti. 1999. A functional role for ezrin during Shigella flexneri entry into epithelial cells. J. Cell Sci. 112: 2059– 2068.

58. Steinhauer, J.,, R. Agha,, T. Pham,, A. W. Varga,, and M. B. Goldberg. 1999. The unipolar Shigella surface protein IcsA is directly targeted to the old pole; IcsP cleavage of IcsA occurs over the entire bacterial surface. Mol. Microbiol. 32: 367– 378.

59. Suzuki, T.,, M.-C. Lett,, and C. Sasakawa. 1995. Extracellular transport of VirG protein in Shigella. J. Biol. Chem. 270: 30874– 30880.

60. Suzuki, T.,, H. Miki,, T. Takenawa,, and C. Sasakawa. 1998. Neural Wiskott-Aldrich syndrome protein is implicated in the actin-based motility of Shigella flexneri. EMBO J. 17: 2767– 2776.

61. Tran Van Nhieu, G.,, A. Ben-Ze’ev,, and P. J. Sansonetti. 1997. Modulation of bacterial entry into epithelial cells by association between vinculin and the Shigella IpaA invasin. EMBO J. 16: 2717– 2729.

62. Tran Van Nhieu, G.,, E. Caron,, A. Hall,, and P. J. Sansonetti. 1999. IpaC induces actin polymerization and filopodia formation during Shigella entry into epithelial cells. EMBO J. 18: 3249– 3262.

63. 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.

64. Watanabe, H.,, E. Arakawa,, K.-I. Ito,, J.-I. Kato,, and A. Nakamura. 1990. Genetic analysis of an invasion region by use of a Tn 3-lac transposon and identification of a second positive regulator gene, invE, for cell invasion of Shigella sonnei: significant homology of InvE with ParB of plasmid P1. J. Bacteriol. 172: 619– 629.

65. Watarai, M.,, S. Funato,, and C. Sasakawa. 1996. Interaction of Ipa proteins of Shigella flexneri with α5β1 integrin promotes entry of the bacteria into mammalian cells. J. Exp. Med. 183: 991– 999.

66. Zychlinsky, A.,, J. J. Perdomo,, and P. J. Sansonetti. 1994. Molecular and cellular mechanisms of tissue invasion by Shigella flexneri. Ann. N. Y. Acad. Sci. 730: 197– 208.

67. Zychlinsky, A.,, K. Thirumalai,, J. Arondel,, J. Cantey,, A. Aliprantis,, and P. Sansonetti. 1996. In vivo apoptosis in Shigella flexneri infections. Infect. Immun. 64: 5357– 5365.