Invasion of Epithelial Cells by Bacterial Pathogens

The Paradigm of Shigella
  • Kirsten Niebuhr
  • Philippe J. Sansonetti
Part of the Subcellular Biochemistry book series (SCBI, volume 33)


A necessary step in the successful colonization and production of disease by microbial pathogens is their ability to persist in the host. Pathogenic bacteria have achieved this goal by developing mechanisms to adhere to mucosal surfaces or, going even further, by entering into and surviving within eukaryotic cells. Shigella is a well-studied example of a facultative intracellular bacterium that is able to enter into non-professional phagocytes and disseminate in the infected tissue. Thus, Shigella infection can be used as a model system to study the complex interplay between host and pathogen that occurs during the process of disease. In this review, we will discuss how the unraveling of the molecular mechanisms underlying this lifestyle can help to understand and combat the disease caused by this pathogen and provide insights into basic host cell functions that are exploited by the bacterium.


Actin Filament Focal Adhesion Kinase Listeria Monocytogenes Actin Polymerization Shigella Flexneri 
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  1. Adam, T., Arpin, M., Prévost, M.C., Gounon, P., and Sansonetti, P.J., 1995, Cytoskeletal rearrangements and the functional role of T-plastin during entry of Shigella flexneri into HeLa cells, J. Cell Biol. 129: 367–381.PubMedGoogle Scholar
  2. Adam, T., Giry, M., Boquet, P., and Sansonetti, P.J., 1996, Rho-dependent membrane folding causes Shigella entry into epithelial cells, EMBO J. 15: 3315–3321.PubMedGoogle Scholar
  3. Allaoui, A., Sansonetti, P.J., and Parsot, C., 1992, MxiJ, a lipoprotein involved in secretion of Shigella Ipa invasin, is homologous to YscJ, a secretion factor of the Yersinia Yop proteins, J. Bacteriol. 174: 7661–7669.PubMedGoogle Scholar
  4. Allaoui, A., Sansonetti, P.J., and Parsot, C., 1993a, MxiD: an outer membrane protein neces- sary for the secretion of the Shigella flexneri Ipa invasins, Mol. Microbiol. 7: 59–68.PubMedGoogle Scholar
  5. Allaoui, A., Sansonetti, P.J., and Parsot, C., 1993b, Characterization of the Shigella flexneri ipgD and ipgF genes, which are located in the proximal part of the mxi locus, Infect. Immun. 61: 1707–1714.PubMedGoogle Scholar
  6. Allaoui, A., Sansonetti, P.J., Ménard, R., Barzu, S., Mourinier, J., Phalipon, A., and Parsot, C., 1995, MxiG, a membrane protein required for secretion of Shigella invasins: involvement in entry into epithelial cells and intracellular dissemination, Mol. Microbiol. 17: 461–470.PubMedGoogle Scholar
  7. Aktories, K., Braun, S., Rösener, S., Just, I., and Hall, A., 1989, The rho gene product expressed in E. coli is a substrate for botulinum ADP-ribosyltransferase C3, Biochem. Biophys. Res. Commun. 158: 209–213.PubMedGoogle Scholar
  8. Andrews, G.P., and Maurelli, A.T., 1992, mxiA of Shigella flexneri 2a, which faciliates export of invasion plasmid antigens, encodes a homolog of the low-calcium response protein, LcrD, of Yersinia pestis, Infect. Immun. 60: 3287–3295.PubMedGoogle Scholar
  9. Andrews, G.P., Horomockyj, A.E., Coker, C., and Maurelli, A.T., 1991, Vo novel virulence loci, mxiA and mxiB, in Shigella flexneri 2a faciliate excretion of invasion plasmid antigens, Infect. Immun. 59: 1997–2005.PubMedGoogle Scholar
  10. Aspenström, R, Lindberg, U., and Hall, A., 1996, Two GTPases, Cdc42 and Rac, bind directly to a protein implicated in the immunodeficiency disorder Wiskott-Aldrich syndrome, Curr. BioL 6: 70–75.PubMedGoogle Scholar
  11. Arends, M.J., and Wyllie, A.H., 1991, Apoptosis: mechanisms and role in pathology, Int. Rev. Exp. PathoL 32: 223–254.PubMedGoogle Scholar
  12. Bahrani, F.K., Sansonetti, P.J., and Parsot, C., 1997, Secretion of Ipa proteins by Shigella flexneri: inducing molecules and kinetics of activation, Infect. Immun. 65: 4005–4010.PubMedGoogle Scholar
  13. Barzu, S., Benjelloun-Touimi, Z., Phalipon, A., Sansonetti, P.J., and Parsot, C., 1997, Functional analysis of the Shigella flexneri IpaC invasin by insertional mutagenesis, Infect. Immun. 65: 1599–1605.PubMedGoogle Scholar
  14. Bear, J.E., Rawls, J.F., and Saxe, C. III., 1998, SCAR, a WASP-related protein, isolated as a suppressor of receptor defects in late Dictyostelium development, J. CelL Biol. 142: 1325–1335.PubMedGoogle Scholar
  15. Bernardini, M.L., Mounier, J., d’Hauteville, H., Coquis-Rondon, M., and Sansonetti, P.J., 1989, Identification of icsA, a plasmid locus of Shigella flexneri which governs bacterial intra-and intercellular spread through interaction with F-actin, Proc. Natl. Acad. Sci. USA 86: 3867–3871.PubMedGoogle Scholar
  16. Brenner, D.J., Fanning, G.R., Miklos, G.V., and Steigerwalt, A.G., 1973, Polynucleotide sequence relatedness among Shigella species, Int. J. Syst. Bacteriol. 23: 1–7.Google Scholar
  17. Burridge, K., and Chrzanowska-Wodnicka, M., 1996, Focal adhesions, contractility and signalling, Annu. Rev. Cell Dey. Biol. 12: 463–519.Google Scholar
  18. Calalb, M.B., Polte, T.R., and Hanks, S.K., 1995, Tyrosine phosphorylation of focal adhesion kinase at sites in the catalytic domain regulates kinase activity: a role for the Src family kinases, Mol. Cell Biol. 15: 954–963.PubMedGoogle Scholar
  19. Carpenter, P.B., Zuberi, A.R., and Ordal, G.W., 1993, Bacillus subtilis flagellar proteins FliP, FliQ, FIiR and FlhB are related to Shigella flexneri virulence factors, Gene 137: 243–245.Google Scholar
  20. Chakraborty, T., Ebel, F, Domann, E., Niebuhr, K., Gerstel, B., Pistor, S., Temm-Grove, C.J., Jockush, B.M., Reinhard, M., Walter, U., and Wehland, J., 1995, A focal adhesion factor directly linking intracellularly motile Listeria monocytogenes and Listeria ivanovii to the actin based cytoskeleton of mammalian cells, EMBO J. 14: 1314–1321.PubMedGoogle Scholar
  21. Chen, H.C., Appeddu, P.A., Parsons, J.T., Hildebrand, J.D., Schaller, M.D., and Guan, J.L.,1995, Interaction of focal adhesion kinase with the cytoskeletal protein talin, J. BioL Chem. 270: 16995–16999.Google Scholar
  22. Chen, Y., Smith, M.R., Thirumalai, K., and Zychlinsky, A., 1996, A bacterial invasin induces macrophage apoptosis by binding directly to ICE, EMBO J. 15: 3853–3860.PubMedGoogle Scholar
  23. Clerc, R, and Sansonetti, P.J., 1987, Entry of Shigella flexneri into HeLa cells: evidence for directed phagocytosis involving actin polymerization and myosin accumulation, Infect. Immun. 55: 2681–2688.PubMedGoogle Scholar
  24. Cornelis, G.R., 1998, The Yersinia deadly kiss, J. BacterioL 180: 5495–5504.PubMedGoogle Scholar
  25. Cornelis, G.R., and Wolf-Watz, H., 1997, The Yersinia Yop virulon, a bacterial system for subverting eukaryotic cells, Mol. MicrobioL 23: 861–867.PubMedGoogle Scholar
  26. Cossart, R, Boquet, R, Normark, S., and Rappuoli, R., 1996, Cellular microbiology emerging, Science 271 (5247): 315–316.PubMedGoogle Scholar
  27. De Geyter, C., Vogt, B., Benjelloun-Touimi, Z., Sansonetti, P.J., Ruysschaert, J.-M., Parsot, C., and Cabiaux, V., 1997, Interaction of IpaC, a protein involved in entry of S flexneri into epithelial cells, with lipid membranes, FEBS Letter 400: 149–154.Google Scholar
  28. Dehio, C., Prévost, M.C., and Sansonetti, P.J., 1995, Invasion of epithelial cells by Shigella flexneri induces tyrosine phosphorylation of cortactin by a pp60 mediated signalling pathway, EMBO J. 14: 2471–2482.PubMedGoogle Scholar
  29. Derry, J.M.J., Ochs, H.J., and Francke, U., 1994, Isolation of a novel gene mutated in WiskottAldrich Syndrome, Cell 78: 635–644.PubMedGoogle Scholar
  30. Duménil, G., Olivo, J.C., Pellegrini, S., Fellows, M., Sansonetti, P.J., and Tran Van Nhieu, G., 1998, Interferon a inhibits a Src-mediated pathway necessary for Shigella-induced cytoskeletal rearrangements in epithelial cells, J. Cell Biol. 143 :1–10.Google Scholar
  31. Demers, B., Sansonetti, P.J., and Parsot, C., 1998, Induction of type III secretion in Shigella flexneri is associated with differential control of transcription of genes encoding secreted proteins, EMBO J. 17: 2894–2903.PubMedGoogle Scholar
  32. Domann, E., Wehland, J., Rohde, M., Pistor, S., Hartl, M., Goebel, W., Leimeister-Wächter, M., Wuenscher, M., and Chakraborty, T., 1992, A novel bacterial virulence gene in Listeria monocytogenes required for host cell microfilament interaction with homology to the proline-rich region of vinculin, EMBO J. 11: 1981–1990.PubMedGoogle Scholar
  33. DuPont, H.L., Levine, M.M., Hornick, R.B., and Formal, S.B., 1989, Inoculum size in shigellosis and impliations for expected mode of transmission, J. Infect. Dis. 159: 1126 1128.Google Scholar
  34. Dramsi, S., and Cossart, P., 1998, Intracellular pathogens and actin cytoskeleton, Ann. Rev. Cell Dey. Biol. 14: 137–166.Google Scholar
  35. Egile, C., d’Hauteville, H., Parsot, C., and Sansonetti, P.J., 1997, SopA, the outer membrane protease responsible for polar localization of IcsA in Shigella flexneri, Mol. Microbiol. 23: 1063–1074.PubMedGoogle Scholar
  36. Fallman, M., Andersson, K., Hakansson, S., Magnusson, K.E., Stendahl, O., and Wolf-Watz, H., 1995, Yersinia pseudotuberculosis inhibits Fc receptor-mediated phagocytosis in J774 cells, Infect. Immun. 63: 3117–3124.Google Scholar
  37. Finchan, V.J., Unlu, M., Brunton, V.G., Pitts, J.D., Wyke, J.A., and Frame, M.C., 1996, Translocation of src kinase to the cell periphery is mediated by the actin cytoskeleton under the control of the rho family of small G proteins, J. Cell Biol. 135: 1551–1564.Google Scholar
  38. Finlay, B.B., and Falkow, S., 1990, Salmonella interactions with polarized human intestinal Caco-2 epithelial cells, J. Infect. Dis. 162: 1096–1106.PubMedGoogle Scholar
  39. Francis, C.L., Ryan, T.A., Jones, B.D., Smith, S.J., and Falkow, S., 1993, Ruffles induced by Salmonella and other stimuli direct micropinocytosis of bacteria, Nature 364: 639–642.PubMedGoogle Scholar
  40. Fukuda, I., Suzuki, T., Munakata, H., Hayashi, N., Katayama, E., Yoshikawa, M., and Sasakawa, C., 1995, Cleavage of Shigella surface protein VirG occurs at a specific site, but the secretion is not essential for intracellular spreading, J. Bact. 177: 1719–1726.PubMedGoogle Scholar
  41. Gaillard, J.L., Berche P., Frehel, C., Gouin, E., and Cossart, P., 1991, Entry of L. monocytogenes into cells is mediated by internalin, a repeat protein reminiscent of surface antigens from gram-posistive cocci, Cell 65: 1127–1141.PubMedGoogle Scholar
  42. Gertler, F.B., Niebuhr, K., Reinhard, M., Wehland, J., and Soriano, P., 1996, Mena, a relative of VASP and Drosophila Enabled, is implicated in the control of microfilament dynamics, Cell 87: 227–239.PubMedGoogle Scholar
  43. Goldberg, M.B., 1997, Shigella actin-based motility in the absence of vinculin, Cell. Motil. Cytoskeleton 37: 44–53.PubMedGoogle Scholar
  44. Goldberg, M.B., and Sansonetti, P.J., 1993, Shigella subversion of the cellular cytoskeleton: a strategy for epithelial colonization, Infect. Immun. 61: 4941–4946.PubMedGoogle Scholar
  45. Goldberg, M.B., and Theriot, A.J., 1995, Shigella flexneri surface protein IcsA is sufficient to direct actin-based motility, Proc. Natl. Acad. Sci. USA 92: 6572–6576.Google Scholar
  46. Goldberg, M.B., Barzu, O., Parsot, C., and Sansonetti, P.J., 1993, Unipolar localization and ATPase activity of IcsA, a Shigella flexneri protein involved in intracellular movement, Infect. Immun. 175: 2189–2196.Google Scholar
  47. Goldberg, M.B., Theriot, J.A., and Sansonetti, P.J.,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.Google Scholar
  48. Groisman, E.A., and Ochman, H., 1993, Cognate gene clusters govern invasion of host epithe- lial cells by Salmonella typhimurium and Shigella flexneri, EMBO J. 12: 3779–3787.PubMedGoogle Scholar
  49. Guichon, A., and Zychlinsky, A., 1997, Clinical isolates of Shigella species induce apoptosis in macrophages, J. Infect. Dis. 175: 470–473.PubMedGoogle Scholar
  50. d’Hauteville, H., and Sansonetti, P.J., 1992, Phosphorylation of IcsA by cAMP-dependent protein kinase and its effect on intercellular spread of Shigella flexneri, Mol. Microbiol. 6: 833–841.PubMedGoogle Scholar
  51. d’Hauteville, H., Dufourcq-Lagelouse, R., Nato, F, and Sansonetti, P.J., 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.PubMedGoogle Scholar
  52. Hermant, D., Ménard, R., Arricau, N., Parsot, C., and Popoff, M.Y., 1995, Functional conservation of the Salmonella and Shigella effectors in entry into epithelial cells, Mol. Microbiol. 17: 781–789.PubMedGoogle Scholar
  53. High, N., Mounier, J., Prévost, M.C., and Sansonetti, P.J., 1992, IpaB of Shigella flexneri causes entry into epithelial cells and escape from the phagocytic vacuole, EMBO J. 11: 1991–1999.PubMedGoogle Scholar
  54. Hilbi, H.J., Moss, E., Hersh, D., Chen, Y., Arondel, J., Banerjee, R.A., Flavell, J., Yuan, J., Sansonetti, P.J., and Zychlinsky, A., 1998, Shigella-induced apoptosis is dependent on Caspase-1 which binds to IpaB, J. Biol. Chem. 273: 3 2864.Google Scholar
  55. Isberg, R.R., and Leong, J.M., 1990, Multiple 11 chain integrins are receptors for invasin, a protein that promotes bacterial penetration into mammalian cells, Cell 60: 861–871.PubMedGoogle Scholar
  56. Islam, D., Veress, B., Bardhan, P.K., Lindberg, A.A., and Christensson, B., 1997, In situ characterization of inflammatory responses in the rectal mucosae of patients with shigellosis, Infect. Immun. 65: 739–749.Google Scholar
  57. Just, I., Selzer, J., Wilm, M., von Eichel-Streiber, C., and Aktories, K., 1995, Glucosylation of Rho proteins by Clostridium difficile toxin B, Nature 375: 500–503.PubMedGoogle Scholar
  58. Klausner, T., Pohlner, J., and Meyer, T.F., 1993, The secretion pathway of IgA protease-type proteins in gram-negative bacteria, Bioessays 15: 799–805.Google Scholar
  59. Kocks, C., Gouin, E., Tabouret, M., Berche, P., Ohayon, H., and Cossart, P., 1992, Listeria monocytogenes-induced actin assembly requires the actA gene product, a surface protein, Cell 68: 521–531.Google Scholar
  60. Kocks, C., Marchand, J.B., Gouin, E., d’Hauteville, H., Sansonetti, P.J., Carlier, M.F., and Cossart, P., 1995, The unrelated surface proteins ActA of Listeria monocytogenes and IcsA of Shigella flexneri are sufficient to confer actin-based motility to L. innocua and E. coli respectively, Mol. Microbiol. 18: 413–423.PubMedGoogle Scholar
  61. Kotloff, K.L., Winickoff, J.P., Ivanoff, B., Clemens, J.D., Swerdlow, D.L., Sansonetti, P.J., Adak, G.K., and Levine, M.M., Global burden of Shigella infections: implication for vaccine development and implementation, WHO Bulletin. (in press).Google Scholar
  62. Kozma, R., Ahmed, S., Best, A., and Lim, L., 1995, The Ras-related protein Cdc42Hs and bradykinin promote formation of peripheral actin microspikes and filopodia in Swiss3T3 fibroblasts, Mol. Cell Biol. 15: 1942–1949.PubMedGoogle Scholar
  63. Kubori, T., Matsushima, Y, Nakamura, D., Uralil, J., Lara-Tejero, M., Sukhan, A., Galin, J.E., and Aizawa, S.-I., 1998, Supermolecular structure of the Salmonella typhimurium type III protein secretion system, Science 280: 602–605.PubMedGoogle Scholar
  64. LaBrec, E.H., Schneider, H., Magnani, T.J., and Formal, S.B., 1964, Epithelial cell penetration as an essential step in the pathogenesis of bacillary dysentery, J. Bacteriol. 88: 1503–1518.PubMedGoogle Scholar
  65. Laine, R.O., Zeile, W., Kang, F., Purich, D.L., and Southwick, F.S., 1997, Vinculin proteolysis unmasks an ActA homolog for actin-based Shigella motility, J. Cell. Biol. 138: 1255–1264.PubMedGoogle Scholar
  66. Lasa, I., David, V., Gouin, E., Marchand, J.-B., and Cossart, P., 1995, The N-terminal part of ActA is critical for the actin-based motility of Listeria monocytogenes; the central prolinerich region acts as a stimulator, Mol. Microbiol. 18: 425–426.PubMedGoogle Scholar
  67. Lett, M.C., Sasakawa, C., Okada, N., Sakai, T., Makino, S., Yamada, M., Komatsu, K., and Yoshikawa, M., 1988, VirG, a plasmid-coded virulence gene of Shigella flexneri: identification of the VirG protein and determination of the complete coding sequence, J. Bacteriol. 171: 353–359.Google Scholar
  68. Lo, S.H., and Chen, L.B., 1994, Focal adhesion as a signal transduction organelle, Cancer Metastasis Rev. 13: 9–24.PubMedGoogle Scholar
  69. Machesky, L.M., and Hall, A., 1997, Role of actin polymerization and adhesion to extracellular matrix in Rac-and Rho-induced cytoskeletal reorganization, J. Cell Biol. 138: 913–926.PubMedGoogle Scholar
  70. Machesky, L.M., and Insall, R.H., 1998, Scarl and the related Wiskott-Aldrich syndrome protein, WASP, regulate the actin cytoskeleton through the Arp2/3 complex, Curr. Biol. 8: 1347–1356.PubMedGoogle Scholar
  71. Mahida, Y.R., Patel, S., Gionchetti, P., Vaux, D., and Jewell, D.P., 1989, Macrophage subpopulations in lamina propria of normal and inflamed colon and terminal ileum, Gut 30: 826–834.PubMedGoogle Scholar
  72. Makino, S., Sasakawa, C., Kamata, K., Kurata, T., and Yoshikawa, M., 1986, A genetic determinant required for continuous reinfection of adjacent cells on large plasmid in S. flexneri 2a, Cell 46: 551–555.PubMedGoogle Scholar
  73. Mantis, N., Prévost, M.C., and Sansonetti, P.J., 1996, Anaysis of epithelial cell stress responses during infection by Shigella flexneri, Infect. Immun. 64: 2474–2482.PubMedGoogle Scholar
  74. Maurelli, A.T., Baudry, B., d’Hauteville, H., Hale, T.L., and Sansonetti, P.J., 1985, Cloning of plasmid DNA sequences involved in invasion of HeLa cells by Shigella flexneri, Infect. Immun. 49: 164–171.PubMedGoogle Scholar
  75. Ménard, R., Sansonetti, P.J., and Parsot, C., 1993, Non polar mutagenesis of the ipa genes defines IpaB, IpaC and IpaD as effectors of Shigella flexneri entry into epithelial cells, J. Bacteriol. 175: 5899–5906.PubMedGoogle Scholar
  76. Ménard, R., Sansonetti, P.J., and Parsot, C., 1994a, The secretion of the Shigella flexneri Ipa invasins is induced by the epithelial cell and controlled by IpaB and IpaD, EMBO J. 13: 5293–5302.PubMedGoogle Scholar
  77. Ménard, R., Sansonetti, P.J., Parsot, C., and Vasselon, T., 1994b, Extracellular association and cytoplasmic partitioning of the IpaB and IpaC invasins of Shigella flexneri, Cell 79: 515–525.PubMedGoogle Scholar
  78. Ménard, R., Prévost, M.C., Gounon, P., Sansonetti, P.J., and Dehio, C., 1996, The secreted Ipa complex of Shigella flexneri promotes entry into mammalian cells, Proc. Natl. Acad. Sci. USA 93: 1254–1258.PubMedGoogle Scholar
  79. Mengaud, J., Ohayon, H., Gounon, P., Mage, R.M., and Cossart, P., 1995, E-cadherin is the receptor for internalin, a surface protein required for entry of L. monocytogenes into epithelial cells, Cell 84: 923–932.Google Scholar
  80. Miki, H., Miura, K., and Takenawa, T., 1996, N-WASP, a novel actin-depolymerizing protein regulates the cortical cytoskeletal rearrangements in a PIP2-dependent manner downstream of tyrosine kinases, EMBO J. 15: 5326–5335.PubMedGoogle Scholar
  81. Miki, H., Suetsugu, S., and Takenawa, T., 1998, WAVE, a novel WASP-family protein involved in actin reorganization induced by Rac, EMBO J. 17: 6932–6941.PubMedGoogle Scholar
  82. Miki, H., Sasaki, T., Takai, Y., and Takenawa, T.,1998, Induction of filopodium formation by a WASP-related actin-depolymerizing protein N-WASP, Nature 391: 93–96.Google Scholar
  83. Mounier, J., Vasselon, T., Hellio, R., Lesourd, M., and Sansonetti, P.J., 1992, Shigella flexneri enters human colonic Caco-2 epithelial cells through their basolateral pole, Infect. Immun. 60: 237–248.Google Scholar
  84. Mullins, R.D., Heuser, J.A., and Pollard, T.D., 1998, The interaction of Arp2/3 complex with actin: nucleation, high affinity pointed end capping, and formation of branching networks of filaments, Proc. Natl. Acad. Sci. USA 95: 6181–6186.PubMedGoogle Scholar
  85. Niebuhr, K., Ebel, E, Ronald, E, Reinhard, M., Domann, E., Carl, U.D., Ulrich, W., Gertler, F.B., Wehland, J., and Chakraborty, T., 1997, A novel proline-rich motif present in ActA of Listeria monocytogenes and cytoskeletal proteins is the ligand for the EVH1 domain, a protein module present in the Ena/VASP family, EMBO J. 16: 2793–2802.Google Scholar
  86. Nobes, C.D., and Hall, A., 1995, GTPases regulate the assembly of multimolecular focal com- plexes associated with actin stress fibers, lamellipodia and filopodia, Cell 81: 53–62.PubMedGoogle Scholar
  87. Oaks, E.V., Hale,T.L., and Formal, S.B., 1986, Serum immune response to Shigella protein antigens in rhesus monkeys and humans infected with Shigella spp., Infect. Immun. 53: 57–63.Google Scholar
  88. Ogawa, H., Nakamura, A., and Nakaya, R., 1968, Cinemicrographic study of tissue cell cultures infected with Shigella flexneri, Jpn. J. Med. Sci. Biol. 21: 259–273.PubMedGoogle Scholar
  89. Parsot, C., Ménard, R., Gounon, P., and Sansonetti, P.J., 1995, Enhanced secretion through the Shigella flexneri Mxi-Spa translocon leads to assembly of extracellular proteins into macromolecular structures, Mol. Microbiol. 16: 291–300.PubMedGoogle Scholar
  90. Perdomo, J.J., Gounon, P., and Sansonetti, P.J., 1994a, Polymorphonuclear leukocyte transmigration promotes invasion of colonic epithelial monolayer by Shigella flexneri, J. Clin. Invest. 93: 633–643.PubMedGoogle Scholar
  91. Perdomo, J.J., Cavaillon, J.M., Huerre, M., Ohayon, H., Gounon, P., and Sansonetti, P.J.,1994b, Acute inflammation causes epithelial invasion and mucosal destruction in experimental shigellosis, J. Exp. Med. 180: 1307–1319.Google Scholar
  92. Pistor, S., Chakraborty, T., Walter, U., and Wehland, J., 1995, The bacterial actin nucleator protein ActA of Listeria monocytogenes contains multiple binding sites for host microfilament proteins, Curr. Biol. 5: 517–525.PubMedGoogle Scholar
  93. Pollard, T.D., 1995, Missing link for intracellular bacterial movement ? Curr. Biol. 5: 837–840.PubMedGoogle Scholar
  94. Prévost, M.C., Lesourd, M., Arpin, M., Vernel, E, Mounier, J., Hellio, R., and Sansonetti, 1992, Unipolar reorganisation 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.PubMedGoogle Scholar
  95. Rajakumar, K., Jost, B.H., Sasakawa, C., Okada, N., Yoshikawa, M., and Adler, B., 1994, Nucleotide sequence of the rhamnose biosynthetic operon of Shigella flexneri 2a and role of lipopolysaccharide in virulence, J. Bacteriol. 176: 2362–2373.PubMedGoogle Scholar
  96. Ridley, Al, and Hall, A., 1992, The small GTP-binding protein Rho regulates the assembly of focal adhesives and actin stress fibers in response to growth factors, Cell 70: 389–399.PubMedGoogle Scholar
  97. Ridley, A.J., Paterson, H.F., Johnston, C., and Hall, A., 1992, The small GTP-binding protein Rac regulates growth factor induced membrane ruffling, Cell 70: 401–410.PubMedGoogle Scholar
  98. Rivero-Lezcano, O.M., Macilla, A., Sameshima, J.H., and Robbins, K.C., 1995, Wiskott-Aldrich syndrome protein physically associates with Nck through Src homology domains, Mol. Cell Biol. 15: 5725–5731.PubMedGoogle Scholar
  99. Rosqvist, R., Forsberg, A., Rimpiläinen, M, and Wolf-Watz, H., 1990, The cytotoxic protein YopE of Yersinia obstructs the primary host defence, Mot. Microbiol. 4: 657–667.Google Scholar
  100. Rosqvist, R., Forsberg, A., and Wolf-Watz, H., 1991, Intracellular targeting of the Yersinia YopE cytotoxin in mammalian cells induces actin microfilament disruption, Infect. Immun. 59: 4562–4569.PubMedGoogle Scholar
  101. Rosqvist, R., Magnusson, K.E., and Wolf-Watz, H., 1994, Target cell contact triggers expression and polarized transfer of Yersinia YopE cytotoxin into mammalian cells, EMBO J. 13: 964–972.PubMedGoogle Scholar
  102. Rosqvist, R., Hakansson, S., Forsbery, 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: 4187–4195.PubMedGoogle Scholar
  103. Sandlin, R.C., Lampe!, K.A., Keasler, S.P., Goldberg, M.B., Stolzer, A.L., and Maurelli, A.T., 1995, Avirulence of rough mutants of Shigella flexneri: requirement of O antigen for correct unipolar localization of IcsA in the bacterial outer membrane, Infect. Immun. 63: 229–237.PubMedGoogle Scholar
  104. Sansonetti, P.J., Kopecko, D.J., and Formal, S.B., 1982, Involvement of a large plasmid in the invasive ability of Shigella flexneri, Infect. Immun. 35: 852–860.PubMedGoogle Scholar
  105. Sansonetti, P.J., Ryter, A., Clerc P., Maurelli, A.T., and Mounier, J., 1986, Multiplication of Shigella flexneri within HeLa cells: lysis of the phagocytic vacuole and plasmid-mediated contact hemolysis, Infect. Immun. 51: 461–469.PubMedGoogle Scholar
  106. Sansonetti, P.J., Arondel, J., Fontaine, A., d’Hauteville, H., and Bernardini, M.L., 1991, ompB (osmo-regulation) and icsA (cell to cell spread) mutants of Shigella flexneri: vaccine candidates and probes to study the pathogenesis of shigellosis, Vaccine 9: 416–422.Google Scholar
  107. Sansonetti, P.J., Mounier, J., Prévost, M.C., and Mage, R.M., 1994, Cadherin expression is required for the spread of Shigella flexneri between epithelial cells, Cell 76: 829–839.PubMedGoogle Scholar
  108. Sansonetti, P.J., Arondel, J., Cavaillon, J.M., and Huerre, M., 1995, Role of IL-1 in the pathogenesis of experimental shigellosis, J. Clin. Invest. 96: 884–892.PubMedGoogle Scholar
  109. Sansonetti, P.J., Arondel, J., Cantey, R.J., Prévost, M.C., and Huerre, M., 1996, Infection of rabbit Peyer’s patches by Shigella flexneri: effect of adhesive or invasive bacterial phenotypes on follicular-associated epithelium., Infect. Immun. 64: 2752–2764.PubMedGoogle Scholar
  110. Sasakawa, C., Kamata, K., Sakai, T., Makino, S.I., Yamada, M., Okada, N., and Yoshikawa, M., 1988, Virulence associated genetic regions comprising 30 kilobases of the 230-kilobase plasmid in Shigella flexneri 2a, J. Bacteriol. 170: 2480–2484.PubMedGoogle Scholar
  111. Sasakawa, C., Komatsu, K., Tobe, T., Suzuki, T., and Yoshikawa, M., 1993, Eight genes in region 5 that form an operon are essential for invasion of epithelial cells by Shigella flexneri 2a, J. Bacteriol. 175: 2334–2346.PubMedGoogle Scholar
  112. Savill, J., Fadok, V., Henson, P., and Haslett, C., 1993, Phagocyte recognition of cells undergoing apoptosis, Immunol. Today 14: 131–136.PubMedGoogle Scholar
  113. Schaller, M.D., Hildebrand, J.D., Shannon, J.D., Fox, J.W., Vines, R.R., and Parsons, J.T., 1994, Autophosphorylation of the focal adhesion kinase, pp125’, directs SH2-dependent binding of pp60, Mol. Cell. Biol. 14: 1680–1688.PubMedGoogle Scholar
  114. Shere, K.D., Sallustio, S., Manessis, A., d’Aversa, T.G., and Golberg, M.B., 1997, Disruption of IcsP, the major Shigella protease that cleaves IcsA, accelerates actin-based motility, Mol. Microbiol. 25: 451–462.PubMedGoogle Scholar
  115. Simonet, M., Richard, S., and Berche, P., 1990, Electronmicroscopic evidence for in vivo extra-cellular localization of Yersinia pseudotuberculosis harboring the pYV plasmid, Infect. Immun. 58: 841–845.PubMedGoogle Scholar
  116. Soestatyo, M., Biewenga, J., Kraal, G., and Sminia, T., 1990, The localization of macrophage subsets and dendritic cells in the gastrointestinal tract of the mouse with special reference to the presence of high endothelial venules. An immuno-and enzyme-histochemical study, Cell Tissue Res. 259: 587–593.Google Scholar
  117. Sory, M.P., and Cornelis, G.R., 1994, Translocation of a hybrid YopE-adenylate cyclase from Yersinia enterocolitica into Hela cell, Mol. Microbiol. 14: 583–594.PubMedGoogle Scholar
  118. Suzuki, T, Lett, M.C., and Sasakawa, C., 1995, Extracellular tansport of VirG protein in Shigella, J. Biol. Chem. 270: 30874–30880.PubMedGoogle Scholar
  119. Suzuki, T., Shinsuke, S., and Sasakawa, C., 1996, Functional analysis of Shigella VirG domains essential for interaction with vinculin and actin-based motility, J. Chem. Biol. 271: 21878–21885.Google Scholar
  120. Suzuki, T., Miki, H., Takenawa, T., and Sasakawa, C, 1998, Neural Wiskott-Aldrich Syndrome Protein is implicated in the actin-based motility of Shigella flexneri, EMBO J. 17: 2767–2776.PubMedGoogle Scholar
  121. Symons, M., Derry, J.M.J., Karlak, B., Jiang, S., Lemahieu, V., McCormick, E, Francke, U., and Abo, A., 1994, Wiskott-Aldrich Syndrome Protein, a novel effector for the GTPases Cdc42Hs, is implicated in actin polymerization, Cell 84: 723–734.Google Scholar
  122. Theriot, J.A., 1995, The cell biology of infection by intracellular bacterial pathogens, Annu. Rev. Cell. Dev. Biol. 11: 213–239.PubMedGoogle Scholar
  123. Theriot, J.A., Mitchison, Td., Tilney, L.G., and Portnoy, D.A., 1992, The rate of actin-based motility of intracellular Listeria monocytogenes equals the rate of actin polymerization, Nature 357: 257–260.PubMedGoogle Scholar
  124. Thornberry, N.A., and Lazebnik, Y., 1998, Caspases: enemies within, Science 281: 1312–1316.PubMedGoogle Scholar
  125. Tran Van Nhieu, G., Adam, T., Dehio, C., Ménard, R., Skoudy, A., Mounier, J., Hellio, R., Gounon, P., and Sansonetti, P.J., 1997a, Shigella-induced cytoskeletal reorganisation during host cell invasion, in: Molecular aspects of host-pathogen interaction, (M.A. Mc Crae, J.R. Saunders, C.J.Smyth, and N.D. Stow; eds. ), Cambridge University press, pp. 237–252.Google Scholar
  126. Tran Van Nhieu, G., Ben Ze’ev, A., and Sansonetti, P.J., 1997b, Modulation of bacterial entry in epithelial cells by association between vinculin and the Shigella IpaA invasin, EMBO J. 16: 2717–2729.Google Scholar
  127. Iltrner, C.E., and Miller, J.T., 1994, Primary sequenceof paxillin contains putative SH2 and SH3 domain binding motifs and multiple LIM domains: Identification of a vinculin and pp125’-binding region, J. Cell Science 107: 1583–1591.Google Scholar
  128. Van Gisjegem, E, Génin, S., and Boucher, C., 1993, Conservation of secretion pathways for pathogenicity determinants of plant and animal bacteria, Trends Microbiol. 1: 175–180.Google Scholar
  129. Vasselon, T., Mounier, J., Hellio, R., and Sansonetti, P.J., 1992, Movement along actin filaments of the perijunctional area and de novo polymerization of cellular actin are required for Shigella flexneri colonization of epithelial Caco-2 cell monolayers, Infect. Immun. 60: 1031–1040.PubMedGoogle Scholar
  130. Venkatesan, M., Buysse, J.M., and Kopecko, D.J., 1988, Characterization of invasion plasmid antigen (ipaBCD) genes from Shigella flexneri. DNA sequence analysis and control of gene expression, Proc. Natl. Acad. Sci. USA 85: 9317–9321.PubMedGoogle Scholar
  131. Venkatesan, M.M., Buysse, J.M., and Oaks, E.V., 1992, Surface presentation of Shigella flexneri invasion plasmid antigen requires the products of the spa locus, J. Bacteriol. 174: 1990–2001.PubMedGoogle Scholar
  132. Wassef, J., Keren D.F., and Mailloux, J.L., 1989, Role of M cells in initial bacterial uptake and in ulcer formation in the rabbit intestinal loop model in shigellosis, Infect. Immun. 57: 858–863.PubMedGoogle Scholar
  133. Watarai, M., Tobe, T., Yoshikawa, M., and Sasakawa, C., 1995, Contact of Shigella with host cells triggers release of Ipa invasins and is an essential function of invasiveness, EMBO J. 14: 2461–2470.PubMedGoogle Scholar
  134. Watarai, M., Funato, S., and Sasakawa, C., 1996, Interaction of Ipa proteins of Shigella flexneri with alpha5betal integrin promotes entry of the bacteria into mammalian cells, J. Exp. Med. 183: 991–999.Google Scholar
  135. Watarai, M., Kamata, Y., Kozaki, S., and Sasakawa, C., 1997, Rho, a small GTP-binding protein, is essential for Shigella invasion of epithelial cells, J. Exp. Med. 185: 281–292.PubMedGoogle Scholar
  136. Welch, M.D., Iwamatsu, A., and Mitchison, T.J., 1997, Actin polymerization is induced by the Arp2/3 complex at the surface of Listeria monocytogenes, Nature 385: 265–269.PubMedGoogle Scholar
  137. Welch, M.D., Rosenblatt, J., Skoble, J., Portnoy, D.A., and Mitchison, T.J., 1998, Interaction of Arp2/3 complex and the Listeria monocytogenes ActA protein in actin filament nucleation, Science 281: 105–108.PubMedGoogle Scholar
  138. Wu, H., Reynolds, A., Kanner, S., Vines, R., and Parsons, J., 1991, Identification and characterization of a novel cytoskeleton-associated pp60src substrate, Mol. Cell. Biol. 11: 5113–5123.PubMedGoogle Scholar
  139. Young, V.B., Falkow, S., and Schoolnik, G.K., 1992, The invasin protein of Yersinia enterolitica: internalization of invasin-bearing bacteria by eukaryotic cells is associated with reorganization of the cytoskeleton, J. Cell Biol. 116: 197–207.PubMedGoogle Scholar
  140. Zeile, W.L., Purich, D.L., and Southwick, ES., 1996, Recognition of two classes of oligoproline sequences in profilin-mediated acceleration of actin based Shigella motility, J. Cell Biol. 133: 49–59.PubMedGoogle Scholar
  141. Zychlinsky, A., Prévost, M.C., and Sansonetti, P.J., 1992, Shigella flexneri induces apoptosis in infected macrophages, Nature 358: 167–169.Google Scholar
  142. Zychlinsky, A., Fitting, C., Cavaillon, J.M., and Sansonetti, P.J., 1994a, Interleukin-1 is released by macrophages during apoptosis induced by Shigella flexneri, J. Clin. Invest. 94: 1328–1332.PubMedGoogle Scholar
  143. Zychlinsky, A., Kenny, B., Ménard, R., Prévost, M.C., Holland, I.B., and Sansonetti, P.J., 1994b, IpaB mediates macrophage apoptosis induced by Shigella flexneri, Mol. Microbiol. 11: 619–627.PubMedGoogle Scholar
  144. Zychlinsky, A., Thirumalai, K., Arondel, J., Cantey, J.R., Aliprantis, A.O., and Sansonetti, P.J., 1996, In vivo apoptosis in Shigella flexneri infections, Infect. Immun. 64: 5357–5365.PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2000

Authors and Affiliations

  • Kirsten Niebuhr
    • 1
  • Philippe J. Sansonetti
    • 1
  1. 1.Unité de Pathogénie Microbienne Moléculaire Institut PasteurParis Cédex 15France

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