1887

Abstract

Clostridial glucosylating toxins are the main virulence factors of clostridia responsible for gangrene and/or colitis. These toxins have been well characterized to inactivate Rho/Ras-GTPases through glucosylation. However, the signalling pathways downstream of Rho/Ras-GTPases leading to the intracellular effects of these toxins are only partially known. Rac-dependent modification of focal adhesion complexes and phosphoinositide metabolism seem to be key processes involved in actin filament depolymerization and disorganization of intercellular junctions. In addition, clostridial glucosylating toxins induce Rho/Ras-independent intracellular effects such as activation of mitogen-activated protein kinase pathways, which are used by some of these toxins to trigger an inflammatory response.

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2011-08-01
2024-04-19
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References

  1. Aldape M. J., Bryant A. E., Stevens D. L. 2006; Clostridium sordellii infection: epidemiology, clinical findings, and current perspectives on diagnosis and treatment. Clin Infect Dis 43:1436–1446 [View Article][PubMed]
    [Google Scholar]
  2. Aldape M. J., Bryant A. E., Katahira E. J., Hajjar A. M., Finegold S. M., Ma Y., Stevens D. L. 2010; Innate immune recognition of, and response to, Clostridium sordellii . Anaerobe 16:125–130 [View Article][PubMed]
    [Google Scholar]
  3. Al-Mashat R. R., Taylor D. J. 1983a; Production of diarrhoea and enteric lesions in calves by the oral inoculation of pure cultures of Clostridium sordellii . Vet Rec 112:141–146 [View Article][PubMed]
    [Google Scholar]
  4. Al-Mashat R. R., Taylor D. J. 1983b; Clostridium sordellii in enteritis in an adult sheep. Vet Rec 112:19 [View Article][PubMed]
    [Google Scholar]
  5. Arber S., Barbayannis F. A., Hanser H., Schneider C., Stanyon C. A., Bernard O., Caroni P. 1998; Regulation of actin dynamics through phosphorylation of cofilin by LIM-kinase. Nature 393:805–809 [View Article][PubMed]
    [Google Scholar]
  6. Bashour A. M., Fullerton A. T., Hart M. J., Bloom G. S. 1997; IQGAP1, a Rac- and Cdc42-binding protein, directly binds and cross-links microfilaments. J Cell Biol 137:1555–1566 [View Article][PubMed]
    [Google Scholar]
  7. Birukova A. A., Malyukova I., Poroyko V., Birukov K. G. 2007; Paxillin-beta-catenin interactions are involved in Rac/Cdc42-mediated endothelial barrier-protective response to oxidized phospholipids. Am J Physiol Lung Cell Mol Physiol 293:L199–L211 [View Article][PubMed]
    [Google Scholar]
  8. Birukova A. A., Alekseeva E., Cokic I., Turner C. E., Birukov K. G. 2008; Cross talk between paxillin and Rac is critical for mediation of barrier-protective effects by oxidized phospholipids. Am J Physiol Lung Cell Mol Physiol 295:L593–L602 [View Article][PubMed]
    [Google Scholar]
  9. Bishop A. L., Hall A. 2000; Rho GTPases and their effector proteins. Biochem J 348:241–255 [View Article][PubMed]
    [Google Scholar]
  10. Bitti A., Mastrantonio P., Spigaglia P., Urru G., Spano A. I., Moretti G., Cherchi G. B. 1997; A fatal postpartum Clostridium sordellii associated toxic shock syndrome. J Clin Pathol 50:259–260 [View Article][PubMed]
    [Google Scholar]
  11. Bodin S., Giuriato S., Ragab J., Humbel B. M., Viala C., Vieu C., Chap H., Payrastre B. 2001; Production of phosphatidylinositol 3,4,5-trisphosphate and phosphatidic acid in platelet rafts: evidence for a critical role of cholesterol-enriched domains in human platelet activation. Biochemistry 40:15290–15299 [View Article][PubMed]
    [Google Scholar]
  12. Boehm C., Gibert M., Geny B., Popoff M. R., Rodriguez P. 2006; Modification of epithelial cell barrier permeability and intercellular junctions by Clostridium sordellii lethal toxins. Cell Microbiol 8:1070–1085 [View Article][PubMed]
    [Google Scholar]
  13. Braga V. M., Machesky L. M., Hall A., Hotchin N. A. 1997; The small GTPases Rho and Rac are required for the establishment of cadherin-dependent cell-cell contacts. J Cell Biol 137:1421–1431 [View Article][PubMed]
    [Google Scholar]
  14. Braga V. M. M., Del Maschio A., Machesky L., Dejana E. 1999; Regulation of cadherin function by Rho and Rac: modulation by junction maturation and cellular context. Mol Biol Cell 10:9–22[PubMed] [CrossRef]
    [Google Scholar]
  15. Brito G. A. C., Fujji J., Carneiro-Filho B. A., Lima A. A., Obrig T., Guerrant R. L. 2002; Mechanism of Clostridium difficile toxin A-induced apoptosis in T84 cells. J Infect Dis 186:1438–1447 [View Article][PubMed]
    [Google Scholar]
  16. Burridge K., Mangeat P. 1984; An interaction between vinculin and talin. Nature 308:744–746 [View Article][PubMed]
    [Google Scholar]
  17. Burridge K., Wennerberg K. 2004; Rho and Rac take center stage. Cell 116:167–179 [View Article][PubMed]
    [Google Scholar]
  18. Bustelo X. R., Sauzeau V., Berenjeno I. M. 2007; GTP-binding proteins of the Rho/Rac family: regulation, effectors and functions in vivo. Bioessays 29:356–370 [View Article][PubMed]
    [Google Scholar]
  19. Caroni P. 2001; New EMBO members’ review: actin cytoskeleton regulation through modulation of PI(4,5)P(2) rafts. EMBO J 20:4332–4336 [View Article][PubMed]
    [Google Scholar]
  20. Carpenter C. L., Tolias K. F., Van Vugt A., Hartwig J. 1999; Lipid kinases are novel effectors of the GTPase Rac1. Adv Enzyme Regul 39:299–312 [View Article][PubMed]
    [Google Scholar]
  21. Centers for Disease Control and Prevention 2005; Clostridium sordellii toxic shock syndrome after medical abortion with mifepristone and intravaginal misoprostol – United States and Canada, 2001–2005. MMWR Morb Mortal Wkly Rep 54:724[PubMed]
    [Google Scholar]
  22. Chen X., Macara I. G. 2006; Par-3 mediates the inhibition of LIM kinase 2 to regulate cofilin phosphorylation and tight junction assembly. J Cell Biol 172:671–678 [View Article][PubMed]
    [Google Scholar]
  23. Chen M. L., Pothoulakis C., LaMont J. T. 2002; Protein kinase C signaling regulates ZO-1 translocation and increased paracellular flux of T84 colonocytes exposed to Clostridium difficile toxin A. J Biol Chem 277:4247–4254 [View Article][PubMed]
    [Google Scholar]
  24. Clark S. 2003; Sudden death in periparturient sheep associated with Clostridium sordellii . Vet Rec 153:340[PubMed]
    [Google Scholar]
  25. Cohen A. L., Bhatnagar J., Reagan S., Zane S. B., D’Angeli M. A., Fischer M., Killgore G., Kwan-Gett T. S., Blossom D. B. et al. 2007; Toxic shock associated with Clostridium sordellii and Clostridium perfringens after medical and spontaneous abortion. Obstet Gynecol 110:1027–1033 [View Article][PubMed]
    [Google Scholar]
  26. Couzin J. 2006; Infectious disease. RU-486-linked deaths open debate about risky bacteria. Science 312:986 [View Article][PubMed]
    [Google Scholar]
  27. Di Paolo G., Pellegrini L., Letinic K., Cestra G., Zoncu R., Voronov S., Chang S., Guo J., Wenk M. R., De Camilli P. 2002; Recruitment and regulation of phosphatidylinositol phosphate kinase type 1 γ by the FERM domain of talin. Nature 420:85–89 [View Article][PubMed]
    [Google Scholar]
  28. Doughman R. L., Firestone A. J., Anderson R. A. 2003; Phosphatidylinositol phosphate kinases put PI4,5P(2) in its place. J Membr Biol 194:77–89 [View Article][PubMed]
    [Google Scholar]
  29. Dreger S. C., Schulz F., Huelsenbeck J., Gerhard R., Hofmann F., Just I., Genth H. 2009; Killing of rat basophilic leukemia cells by lethal toxin from Clostridium sordellii: critical role of phosphatidylinositide 3′-OH kinase/Akt signaling. Biochemistry 48:1785–1792 [CrossRef]
    [Google Scholar]
  30. Egerer M., Giesemann T., Jank T., Satchell K. J., Aktories K. 2007; Auto-catalytic cleavage of Clostridium difficile toxins A and B depends on cysteine protease activity. J Biol Chem 282:25314–25321 [View Article][PubMed]
    [Google Scholar]
  31. Egerer M., Giesemann T., Herrmann C., Aktories K. 2009; Autocatalytic processing of Clostridium difficile toxin B. Binding of inositol hexakisphosphate. J Biol Chem 284:3389–3395 [View Article][PubMed]
    [Google Scholar]
  32. Ferguson K. M., Lemmon M. A., Schlessinger J., Sigler P. B. 1995; Structure of the high affinity complex of inositol trisphosphate with a phospholipase C pleckstrin homology domain. Cell 83:1037–1046 [View Article][PubMed]
    [Google Scholar]
  33. Fischer M., Bhatnagar J., Guarner J., Reagan S., Hacker J. K., Van Meter S. H., Poukens V., Whiteman D. B., Iton A. et al. 2005; Fatal toxic shock syndrome associated with Clostridium sordellii after medical abortion. N Engl J Med 353:2352–2360 [View Article][PubMed]
    [Google Scholar]
  34. Fukami K., Endo T., Imamura M., Takenawa T. 1994; alpha-Actinin and vinculin are PIP2-binding proteins involved in signaling by tyrosine kinase. J Biol Chem 269:1518–1522[PubMed]
    [Google Scholar]
  35. Fukata M., Kaibuchi K. 2001; Rho-family GTPases in cadherin-mediated cell-cell adhesion. Nat Rev Mol Cell Biol 2:887–897 [View Article][PubMed]
    [Google Scholar]
  36. Fukata M., Nakagawa M., Kuroda S., Kaibuchi K. 1999; Cell adhesion and Rho small GTPases. J Cell Sci 112:4491–4500[PubMed]
    [Google Scholar]
  37. Gaus K., Le Lay S., Balasubramanian N., Schwartz M. A. 2006; Integrin-mediated adhesion regulates membrane order. J Cell Biol 174:725–734 [View Article][PubMed]
    [Google Scholar]
  38. Genth H., Just I. 2010; Functional implications of lethal toxin-catalysed glucosylation of (H/K/N)Ras and Rac1 in Clostridium sordellii-associated disease. Eur J Cell Biol [Epub ahead of print] doi: 10.1016/j.ejcb2010.10.009 [PubMed]
    [Google Scholar]
  39. Genth H., Aktories K., Just I. 1999; Monoglucosylation of RhoA at threonine 37 blocks cytosol-membrane cycling. J Biol Chem 274:29050–29056 [View Article][PubMed]
    [Google Scholar]
  40. Genth H., Dreger S. C., Huelsenbeck J., Just I. 2008; Clostridium difficile toxins: more than mere inhibitors of Rho proteins. Int J Biochem Cell Biol 40:592–597 [View Article][PubMed]
    [Google Scholar]
  41. Geny B., Popoff M. R. 2009; Activation of a c-Jun-NH2-terminal kinase pathway by the lethal toxin from Clostridium sordellii, TcsL-82, occurs independently of the toxin intrinsic enzymatic activity and facilitates small GTPase glucosylation. Cell Microbiol 11:1102–1113 [View Article][PubMed]
    [Google Scholar]
  42. Geny B., Khun H., Fitting C., Zarantonelli L., Mazuet C., Cayet N., Szatanik M., Prevost M. C., Cavaillon J. M., Huerre M. 2007; Clostridium sordellii lethal toxin kills mice by inducing a major increase in lung vascular permeability. Am J Pathol 170:1003–1017 [View Article][PubMed]
    [Google Scholar]
  43. Geny B., Grassart A., Manich M., Chicanne G., Payrastre B., Sauvonnet N., Popoff M. R. 2010; Rac1 inactivation by lethal toxin from Clostridium sordellii modifies focal adhesions upstream of actin depolymerization. Cell Microbiol 12:217–232 [View Article][PubMed]
    [Google Scholar]
  44. Gerhard R., Tatge H., Genth H., Thum T., Borlak J., Fritz G., Just I. 2005; Clostridium difficile toxin A induces expression of the stress-induced early gene product RhoB. J Biol Chem 280:1499–1505 [View Article][PubMed]
    [Google Scholar]
  45. Gilmore A. P., Burridge K. 1996; Regulation of vinculin binding to talin and actin by phosphatidyl-inositol-4-5-bisphosphate. Nature 381:531–535 [View Article][PubMed]
    [Google Scholar]
  46. Golub T., Caroni P. 2005; PI(4,5)P2-dependent microdomain assemblies capture microtubules to promote and control leading edge motility. J Cell Biol 169:151–165 [View Article][PubMed]
    [Google Scholar]
  47. Greene M. F. 2005; Fatal infections associated with mifepristone-induced abortion. N Engl J Med 353:2317–2318 [View Article][PubMed]
    [Google Scholar]
  48. Guo F., Debidda M., Yang L., Williams D. A., Zheng Y. 2006; Genetic deletion of Rac1 GTPase reveals its critical role in actin stress fiber formation and focal adhesion complex assembly. J Biol Chem 281:18652–18659 [View Article][PubMed]
    [Google Scholar]
  49. Halabi-Cabezon I., Huelsenbeck J., May M., Ladwein M., Rottner K., Just I., Genth H. 2008; Prevention of the cytopathic effect induced by Clostridium difficile toxin B by active Rac1. FEBS Lett 582:3751–3756 [View Article][PubMed]
    [Google Scholar]
  50. Hartwig J. H., Bokoch G. M., Carpenter C. L., Janmey P. A., Taylor L. A., Toker A., Stossel T. P. 1995; Thrombin receptor ligation and activated Rac uncap actin filament barbed ends through phosphoinositide synthesis in permeabilized human platelets. Cell 82:643–653 [View Article][PubMed]
    [Google Scholar]
  51. He D., Hagen S. J., Pothoulakis C., Chen M., Medina N. D., Warny M., LaMont J. T. 2000; Clostridium difficile toxin A causes early damage to mitochondria in cultured cells. Gastroenterology 119:139–150 [View Article][PubMed]
    [Google Scholar]
  52. He D., Sougioultzis S., Hagen S., Liu J., Keates S., Keates A. C., Pothoulakis C., LaMont J. T. 2002; Clostridium difficile toxin A triggers human colonocyte IL-8 release via mitochondrial oxygen radical generation. Gastroenterology 122:1048–1057 [View Article][PubMed]
    [Google Scholar]
  53. Hecht G., Pothoulakis C., LaMont J. T., Madara J. L. 1988; Clostridium difficile toxin A perturbs cytoskeletal structure and tight junction permeability of cultured human intestinal epithelial monolayers. J Clin Invest 82:1516–1524 [View Article][PubMed]
    [Google Scholar]
  54. Hecht G., Koutsouris A., Pothoulakis C., LaMont J. T., Madara J. L. 1992; Clostridium difficile toxin B disrupts the barrier function of T84 monolayers. Gastroenterology 102:416–423[PubMed]
    [Google Scholar]
  55. Herrmann C., Ahmadian M. R., Hofmann F., Just I. 1998; Functional consequences of monoglucosylation of Ha-Ras at effector domain amino acid threonine 35. J Biol Chem 273:16134–16139 [View Article][PubMed]
    [Google Scholar]
  56. Ho C. S., Bhatnagar J., Cohen A. L., Hacker J. K., Zane S. B., Reagan S., Fischer M., Shieh W. J., Guarner J., Ahmad S. 2009; Undiagnosed cases of fatal Clostridium-associated toxic shock in Californian women of childbearing age. Am J Obstet Gynecol 201:459.e1–459.e7 [View Article][PubMed]
    [Google Scholar]
  57. Hofmann F., Busch C., Prepens U., Just I., Aktories K. 1997; Localization of the glucosyltransferase activity of Clostridium difficile toxin B to the N-terminal part of the holotoxin. J Biol Chem 272:11074–11078 [View Article][PubMed]
    [Google Scholar]
  58. Hofmann F., Busch C., Aktories K. 1998; Chimeric clostridial cytotoxins: identification of the N-terminal region involved in protein substrate recognition. Infect Immun 66:1076–1081[PubMed]
    [Google Scholar]
  59. Jank T., Aktories K. 2008; Structure and mode of action of clostridial glucosylating toxins: the ABCD model. Trends Microbiol 16:222–229 [View Article][PubMed]
    [Google Scholar]
  60. Janmey P. A., Stossel T. P. 1987; Modulation of gelsolin function by phosphatidylinositol 4,5-bisphosphate. Nature 325:362–364 [View Article][PubMed]
    [Google Scholar]
  61. Johal S. S., Solomon K., Dodson S., Borriello S. P., Mahida Y. R. 2004; Differential effects of varying concentrations of Clostridium difficile toxin A on epithelial barrier function and expression of cytokines. J Infect Dis 189:2110–2119 [View Article][PubMed]
    [Google Scholar]
  62. Jou T. S., Schneeberger E. E., Nelson W. J. 1998; Structural and functional regulation of tight junctions by RhoA and Rac1 small GTPases. J Cell Biol 142:101–115 [View Article][PubMed]
    [Google Scholar]
  63. Just I., Gerhard R. 2004; Large clostridial cytotoxins. Rev Physiol Biochem Pharmacol 152:23–47 [View Article][PubMed]
    [Google Scholar]
  64. Just I., Selzer J., Wilm M., von Eichel-Streiber C., Mann M., Aktories K. 1995a; Glucosylation of Rho proteins by Clostridium difficile toxin B. Nature 375:500–503 [View Article][PubMed]
    [Google Scholar]
  65. Just I., Wilm M., Selzer J., Rex G., von Eichel-Streiber C., Mann M., Aktories K. 1995b; The enterotoxin from Clostridium difficile (ToxA) monoglucosylates the Rho proteins. J Biol Chem 270:13932–13936 [View Article][PubMed]
    [Google Scholar]
  66. Just I., Selzer J., Hofmann F., Green G. A., Aktories K. 1996; Inactivation of Ras by Clostridium sordellii lethal toxin-catalyzed glucosylation. J Biol Chem 271:10149–10153 [View Article][PubMed]
    [Google Scholar]
  67. Kaibuchi K., Kuroda S., Fukata M., Nakagawa M. 1999a; Regulation of cadherin-mediated cell-cell adhesion by the Rho family GTPases. Curr Opin Cell Biol 11:591–596 [View Article][PubMed]
    [Google Scholar]
  68. Kaibuchi K., Kuroda S., Amano M. 1999b; Regulation of the cytoskeleton and cell adhesion by the Rho family GTPases in mammalian cells. Annu Rev Biochem 68:459–486 [View Article][PubMed]
    [Google Scholar]
  69. Kelly C. P., LaMont J. T. 2008; Clostridium difficile – more difficult than ever. N Engl J Med 359:1932–1940 [View Article][PubMed]
    [Google Scholar]
  70. Kim H., Kokkotou E., Na X., Rhee S. H., Moyer M. P., Pothoulakis C., Lamont J. T. 2005a; Clostridium difficile toxin A-induced colonocyte apoptosis involves p53-dependent p21(WAF1/CIP1) induction via p38 mitogen-activated protein kinase. Gastroenterology 129:1875–1888 [View Article][PubMed]
    [Google Scholar]
  71. Kim H., Rhee S. H., Kokkotou E., Na X., Savidge T., Moyer M. P., Pothoulakis C., LaMont J. T. 2005b; Clostridium difficile toxin A regulates inducible cyclooxygenase-2 and prostaglandin E2 synthesis in colonocytes via reactive oxygen species and activation of p38 MAPK. J Biol Chem 280:21237–21245 [View Article][PubMed]
    [Google Scholar]
  72. Kim J. M., Lee J. Y., Yoon Y. M., Oh Y. K., Youn J., Kim Y. J. 2006; NF-kappa B activation pathway is essential for the chemokine expression in intestinal epithelial cells stimulated with Clostridium difficile toxin A. Scand J Immunol 63:453–460 [View Article][PubMed]
    [Google Scholar]
  73. Kim H., Rhee S. H., Pothoulakis C., LaMont J. T. 2009; Clostridium difficile toxin A binds colonocyte Src causing dephosphorylation of focal adhesion kinase and paxillin. Exp Cell Res 315:3336–3344 [View Article][PubMed]
    [Google Scholar]
  74. Kimura A. C., Higa J. I., Levin R. M., Simpson G., Vargas Y., Vugia D. J. 2004; Outbreak of necrotizing fasciitis due to Clostridium sordellii among black-tar heroin users. Clin Infect Dis 38:e87–e91 [View Article][PubMed]
    [Google Scholar]
  75. Kuehne S. A., Cartman S. T., Heap J. T., Kelly M. L., Cockayne A., Minton N. P. 2010; The role of toxin A and toxin B in Clostridium difficile infection. Nature 467:711–713 [View Article][PubMed]
    [Google Scholar]
  76. Lassing I., Lindberg U. 1985; Specific interaction between phosphatidylinositol 4,5-bisphosphate and profilactin. Nature 314:472–474 [View Article][PubMed]
    [Google Scholar]
  77. Lemmon M. A., Ferguson K. M., Abrams C. S. 2002; Pleckstrin homology domains and the cytoskeleton. FEBS Lett 513:71–76 [View Article][PubMed]
    [Google Scholar]
  78. Lewis C. J., Naylor R. 1996; Sudden death in lambs associated with Clostridium sordellii infection. Vet Rec 138:262[PubMed]
    [Google Scholar]
  79. Lewis C. J., Naylor R. D. 1998; Sudden death in sheep associated with Clostridium sordellii . Vet Rec 142:417–421 [View Article][PubMed]
    [Google Scholar]
  80. Ling K., Doughman R. L., Firestone A. J., Bunce M. W., Anderson R. A. 2002; Type I γ phosphatidylinositol phosphate kinase targets and regulates focal adhesions. Nature 420:89–93 [View Article][PubMed]
    [Google Scholar]
  81. Logan M. R., Mandato C. A. 2006; Regulation of the actin cytoskeleton by PIP2 in cytokinesis. Biol Cell 98:377–388 [View Article][PubMed]
    [Google Scholar]
  82. Lyras D., O’Connor J. R., Howarth P. M., Sambol S. P., Carter G. P., Phumoonna T., Poon R., Adams V., Vedantam G. et al. 2009; Toxin B is essential for virulence of Clostridium difficile . Nature 458:1176–1179 [View Article][PubMed]
    [Google Scholar]
  83. Matarrese P., Falzano L., Fabbri A., Gambardella L., Frank C., Geny B., Popoff M. R., Malorni W., Fiorentini C. 2007; Clostridium difficile toxin B causes apoptosis in epithelial cells by thrilling mitochondria. Involvement of ATP-sensitive mitochondrial potassium channels. J Biol Chem 282:9029–9041 [View Article][PubMed]
    [Google Scholar]
  84. McGregor J. A., Soper D. E., Lovell G., Todd J. K. 1989; Maternal deaths associated with Clostridium sordellii infection. Am J Obstet Gynecol 161:987–995[PubMed] [CrossRef]
    [Google Scholar]
  85. Menkel A. R., Kroemker M., Bubeck P., Ronsiek M., Nikolai G., Jockusch B. M. 1994; Characterization of an F-actin-binding domain in the cytoskeletal protein vinculin. J Cell Biol 126:1231–1240 [View Article][PubMed]
    [Google Scholar]
  86. Meyer G. K., Neetz A., Brandes G., Tsikas D., Butterfield J. H., Just I., Gerhard R. 2007; Clostridium difficile toxins A and B directly stimulate human mast cells. Infect Immun 75:3868–3876 [View Article][PubMed]
    [Google Scholar]
  87. Michaelson D., Silletti J., Murphy G., D’Eustachio P., Rush M., Philips M. R. 2001; Differential localization of Rho GTPases in live cells: regulation by hypervariable regions and RhoGDI binding. J Cell Biol 152:111–126 [View Article][PubMed]
    [Google Scholar]
  88. Miech R. P. 2005; Pathophysiology of mifepristone-induced septic shock due to Clostridium sordellii . Ann Pharmacother 39:1483–1488 [View Article][PubMed]
    [Google Scholar]
  89. Murray S., Wooltorton E. 2005; Septic shock after medical abortions with mifepristone (Mifeprex, RU 486) and misoprostol. CMAJ 173:485[PubMed] [CrossRef]
    [Google Scholar]
  90. Nam H. J., Kang J. K., Kim S. K., Ahn K. J., Seok H., Park S. J., Chang J. S., Pothoulakis C., Lamont J. T., Kim H. 2010; Clostridium difficile toxin A decreases acetylation of tubulin, leading to microtubule depolymerization through activation of histone deacetylase 6, and this mediates acute inflammation. J Biol Chem 285:32888–32896 [View Article][PubMed]
    [Google Scholar]
  91. Noritake J., Fukata M., Sato K., Nakagawa M., Watanabe T., Izumi N., Wang S., Fukata Y., Kaibuchi K. 2004; Positive role of IQGAP1, an effector of Rac1, in actin-meshwork formation at sites of cell-cell contact. Mol Biol Cell 15:1065–1076 [View Article][PubMed]
    [Google Scholar]
  92. Nottrott S., Schoentaube J., Genth H., Just I., Gerhard R. 2007; Clostridium difficile toxin A-induced apoptosis is p53-independent but depends on glucosylation of Rho GTPases. Apoptosis 12:1443–1453 [View Article][PubMed]
    [Google Scholar]
  93. Nusrat A., von Eichel-Streiber C., Turner J. R., Verkade P., Madara J. L., Parkos C. A. 2001; Clostridium difficile toxins disrupt epithelial barrier function by altering membrane microdomain localization of tight junction proteins. Infect Immun 69:1329–1336 [View Article][PubMed]
    [Google Scholar]
  94. Ottlinger M. E., Lin S. 1988; Clostridium difficile toxin B induces reorganization of actin, vinculin, and talin in cultured cells. Exp Cell Res 174:215–229 [View Article][PubMed]
    [Google Scholar]
  95. Popoff M. R. 1984; Bacteriological examination in enterotoxaemia of sheep and lamb. Vet Rec 114:324 [View Article][PubMed]
    [Google Scholar]
  96. Popoff M. R., Geny B. 2009; Multifaceted role of Rho, Rac, Cdc42 and Ras in intercellular junctions, lessons from toxins. Biochim Biophys Acta 1788:797–812 [View Article][PubMed]
    [Google Scholar]
  97. Popoff M. R., Stiles B. G. 2006; Bacterial toxins and virulence factors targetting the actin cytoskeleton and intercellular junctions. In The Comprehensive Sourcebook of Bacterial Protein Toxins, 3rd edn. pp. 154–187 Edited by Alouf J. E., Popoff M. R. Amsterdam: Elsevier, Academic Press; [View Article]
    [Google Scholar]
  98. Popoff M. R., Chaves-Olarte E., Lemichez E., von Eichel-Streiber C., Thelestam M., Chardin P., Cussac D., Antonny B., Chavrier P. et al. 1996; Ras, Rap, and Rac small GTP-binding proteins are targets for Clostridium sordellii lethal toxin glucosylation. J Biol Chem 271:10217–10224 [View Article][PubMed]
    [Google Scholar]
  99. Reineke J., Tenzer S., Rupnik M., Koschinski A., Hasselmayer O., Schrattenholz A., Schild H., von Eichel-Streiber C. 2007; Autocatalytic cleavage of Clostridium difficile toxin B. Nature 446:415–419 [View Article][PubMed]
    [Google Scholar]
  100. Richard J. F., Petit L., Gibert M., Marvaud J. C., Bouchaud C., Popoff M. R. 1999; Bacterial toxins modifying the actin cytoskeleton. Int Microbiol 2:185–194[PubMed]
    [Google Scholar]
  101. Richards S. M., Hunt B. W. 1982; Clostridium sordellii in lambs. Vet Rec 111:22 [View Article][PubMed]
    [Google Scholar]
  102. Rørbye C., Petersen I. S., Nilas L. 2000; Postpartum Clostridium sordellii infection associated with fatal toxic shock syndrome. Acta Obstet Gynecol Scand 79:1134–1135[PubMed]
    [Google Scholar]
  103. Rupnik M., Just I. 2006; Large clostridial cytotoxins modifying small GTPases. In The Sourcebook of Bacterial Protein Toxins, 3rd edn. pp. 409–429 Edited by Alouf J. E., Popoff M. R. Amsterdam: Elsevier, Academic Press; [View Article]
    [Google Scholar]
  104. Rupnik M., Pabst S., Rupnik M., von Eichel-Streiber C., Urlaub H., Söling H. D. 2005; Characterization of the cleavage site and function of resulting cleavage fragments after limited proteolysis of Clostridium difficile toxin B (TcdB) by host cells. Microbiology 151:199–208 [View Article][PubMed]
    [Google Scholar]
  105. Sansonetti P. J. 2004; War and peace at mucosal surfaces. Nat Rev Immunol 4:953–964 [View Article][PubMed]
    [Google Scholar]
  106. Sehr P., Joseph G., Genth H., Just I., Pick E., Aktories K. 1998; Glucosylation and ADP ribosylation of rho proteins: effects on nucleotide binding, GTPase activity, and effector coupling. Biochemistry 37:5296–5304 [View Article][PubMed]
    [Google Scholar]
  107. Simonsen A., Stenmark H. 2001; PX domains: attracted by phosphoinositides. Nat Cell Biol 3:E179–E182 [View Article][PubMed]
    [Google Scholar]
  108. Sinave C., Le Templier G., Blouin D., Léveillé F., Deland E. 2002; Toxic shock syndrome due to Clostridium sordellii: a dramatic postpartum and postabortion disease. Clin Infect Dis 35:1441–1443 [View Article][PubMed]
    [Google Scholar]
  109. Songer J. G. 2005; Clostridial diseases in domestic animals. In Handbook on Clostridia pp. 527–542 Edited by Dürre P. Boca Raton: CRC Press, Taylor and Francis Group; [View Article]
    [Google Scholar]
  110. Soper D. E. 1986; Clostridial myonecrosis arising from an episiotomy. Obstet Gynecol 68:Suppl.26S–28S[PubMed]
    [Google Scholar]
  111. Soper D. E. 2007; Abortion and clostridial toxic shock syndrome. Obstet Gynecol 110:970–971 [View Article][PubMed]
    [Google Scholar]
  112. Spiering D., Hodgson L. 2011; Dynamics of the Rho-family small GTPases in actin regulation and motility. Cell Adh Migr 5:170–180 [View Article][PubMed]
    [Google Scholar]
  113. Stecher B., Hardt W. D. 2008; The role of microbiota in infectious disease. Trends Microbiol 16:107–114 [View Article][PubMed]
    [Google Scholar]
  114. Tait A. S., Dalton M., Geny B., D’Agnillo F., Popoff M. R., Sternberg E. M. 2007; The large clostridial toxins from Clostridium sordellii and C. difficile repress glucocorticoid receptor activity. Infect Immun 75:3935–3940 [View Article][PubMed]
    [Google Scholar]
  115. Takaishi K., Sasaki T., Kotani H., Nishioka H., Takai Y. 1997; Regulation of cell-cell adhesion by Rac and Rho small G proteins in MDCK cells. J Cell Biol 139:1047–1059 [View Article][PubMed]
    [Google Scholar]
  116. Tolias K. F., Cantley L. C., Carpenter C. L. 1995; Rho family GTPases bind to phosphoinositide kinases. J Biol Chem 270:17656–17659 [View Article][PubMed]
    [Google Scholar]
  117. Tolias K. F., Hartwig J. H., Ishihara H., Shibasaki Y., Cantley L. C., Carpenter C. L. 2000; Type Iα phosphatidylinositol-4-phosphate 5-kinase mediates Rac-dependent actin assembly. Curr Biol 10:153–156 [View Article][PubMed]
    [Google Scholar]
  118. Van Aelst L., D’Souza-Schorey C. 1997; Rho GTPases and signaling networks. Genes Dev 11:2295–2322 [View Article][PubMed]
    [Google Scholar]
  119. van Rheenen J., Achame E. M., Janssen H., Calafat J., Jalink K. 2005; PIP2 signaling in lipid domains: a critical re-evaluation. EMBO J 24:1664–1673 [View Article][PubMed]
    [Google Scholar]
  120. Vetter I. R., Hofmann F., Wohlgemuth S., Herrmann C., Just I. 2000; Structural consequences of mono-glucosylation of Ha-Ras by Clostridium sordellii lethal toxin. J Mol Biol 301:1091–1095 [View Article][PubMed]
    [Google Scholar]
  121. Voth D. E., Ballard J. D. 2005; Clostridium difficile toxins: mechanism of action and role in disease. Clin Microbiol Rev 18:247–263 [View Article][PubMed]
    [Google Scholar]
  122. Warny M., Keates A. C., Keates S., Castagliuolo I., Zacks J. K., Aboudola S., Qamar A., Pothoulakis C., LaMont J. T., Kelly C. P. 2000; p38 MAP kinase activation by Clostridium difficile toxin A mediates monocyte necrosis, IL-8 production, and enteritis. J Clin Invest 105:1147–1156 [View Article][PubMed]
    [Google Scholar]
  123. Winikoff B. 2006; Clostridium sordellii infection in medical abortion. Clin Infect Dis 43:1447–1448 [View Article][PubMed]
    [Google Scholar]
  124. Yang N., Higuchi O., Ohashi K., Nagata K., Wada A., Kangawa K., Nishida E., Mizuno K. 1998; Cofilin phosphorylation by LIM-kinase 1 and its role in Rac-mediated actin reorganization. Nature 393:809–812 [View Article][PubMed]
    [Google Scholar]
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