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Toxins from bacteria

  • James S. Henkel
  • Michael R. Baldwin
  • Joseph T. Barbieri
Part of the Experientia Supplementum book series (EXS, volume 100)

Abstract

Bacterial toxins damage the host at the site of bacterial infection or distant from the site. Bacterial toxins can be single proteins or oligomeric protein complexes that are organized with distinct AB structure-function properties. The A domain encodes a catalytic activity. ADP ribosylation of host proteins is the earliest post-translational modification determined to be performed by bacterial toxins; other modifications include glucosylation and proteolysis. Bacterial toxins also catalyze the non-covalent modification of host protein function or can modify host cell properties through direct protein-protein interactions. The B domain includes two functional domains: a receptor-binding domain, which defines the tropism of a toxin for a cell and a translocation domain that delivers the A domain across a lipid bilayer, either on the plasma membrane or the endosome. Bacterial toxins are often characterized based upon the secretion mechanism that delivers the toxin out of the bacterium, termed types I–VII. This review summarizes the major families of bacterial toxins and also describes the specific structure-function properties of the botulinum neurotoxins.

Keywords

Diphtheria Toxin Bacterial Toxin Bordetella Pertussis Botulinum Neurotoxin Translocation Domain 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. 1.
    Field M, Graf LH Jr, Laird WJ, Smith PL (1978) Heat-stable enterotoxin of Escherichia coli: In vitro effects on guanylate cyclase activity, cyclic GMP concentration, and ion transport in small intestine. Proc Natl Acad Sci USA 75: 2800–2804PubMedCrossRefGoogle Scholar
  2. 2.
    Giannella RA (1981) Pathogenesis of acute bacterial diarrheal disorders. Annu Rev Med 32: 341–357PubMedCrossRefGoogle Scholar
  3. 3.
    Crane JK, Wehner MS, Bolen EJ, Sando JJ, Linden J, Guerrant RL, Sears CL (1992) Regulation of intestinal guanylate cyclase by the heat-stable enterotoxin of Escherichia coli (STa) and protein kinase C. Infect Immun 60: 5004–5012PubMedGoogle Scholar
  4. 4.
    Takao T, Hitouji T, Aimoto S, Shimonishi Y, Hara S, Takeda T, Takeda Y, Miwatani T (1983) Amino acid sequence of a heat-stable enterotoxin isolated from enterotoxigentic Escherichia coli strain 18D. FEBS Lett 152: 1–5PubMedCrossRefGoogle Scholar
  5. 5.
    Ozaki H, Sato T, Kubota H, Hata Y, Katsube Y, Shimonishi Y (1991) Molecular structure of the toxic domain of heat-stable enterotoxin produced by enterotoxigenic Escherichia coli. J Biol Chem 266: 5934–5941PubMedGoogle Scholar
  6. 6.
    Hidaka Y, Kubota H, Yoshimura S, Ito H, Takeda Y, Shimonishi Y (1988) Disulfide linkages in heat-stable enterotoxin (STp) produced by a porcine strain of enterotoxigenic Escherichia coli. Bull Chem Soc Jpn 61: 1265–1271CrossRefGoogle Scholar
  7. 7.
    Waldman SA, O’Hanley P (1989) Influence of a glycine or proline substitution on the functional properties of a 14-amino acid analog of Escherichia coli heat-stable enterotoxin. Infect Immun 57: 2420–2424PubMedGoogle Scholar
  8. 8.
    Yamasaki S, Sato T, Hidaka Y, Ozaki H, Ito H, Hirayama T, Takeda Y, Sugimura T, Tai A, Shimonishi Y (1990) Structure-activity relationship of Escherichia coli heat-stable enterotoxin: Role of Ala residue at position 14 in toxin-receptor interaction. Bull Chem Soc Jpn 63: 2063–2070CrossRefGoogle Scholar
  9. 9.
    Hasegawa M, Shimonishi Y (2005) Recognition and signal transduction mechanism of Escherichia coli heat-stable enterotoxin and its receptor, guanylate cyclase C. J Peptide Res 65: 261–271CrossRefGoogle Scholar
  10. 10.
    Yoshimura S, Ikemura H, Watanabe H, Aimoto S, Shimonishi Y, Hara S, Takeda T, Miwatani T, Takeda Y (1985) Essential structure for full enterotoxigenic activity of heat-stable enterotoxin produced by enterotoxigenic Escherichia coli. FEBS Lett 181: 138–142PubMedCrossRefGoogle Scholar
  11. 11.
    Ikemura H, Takagi H, Inouye M (1987) Requirement of pro-sequence for the production of active subtilisin E in Escherichia coli. J Biol Chem 262: 7859–7864PubMedGoogle Scholar
  12. 12.
    Gupta DD, Saha S, Chakrabarti MK (2005) Involvement of protein kinase C in the mechanism of action of Escherichia coli heat-stable enterotoxin (STa) in a human colonic carcinoma cell line, COLO-205. Toxicol Appl Pharmol 206: 9–16CrossRefGoogle Scholar
  13. 13.
    Goldstein JL, Sahi J, Bhuva M, Layden TJ, Rao MC (1994) Escherichia coli heat-stable enterotoxin-mediated colonic Cl-secretion is absent in cystic fibrosis. Gastroenterology 107: 950–956PubMedGoogle Scholar
  14. 14.
    Goncalves C, Vachon V, Schwartz JL, Dubreuil JD (2007) The Escherichia coli enterotoxin STb permeabilizes piglet jejunal brush border membrane vesicles. Infect Immun 75: 2208–2213PubMedCrossRefGoogle Scholar
  15. 15.
    Handl CE, Flock JI (1992) STb producing Escherichia coli are rarely associated with infantile diarrhea. J Diarrhoeal Dis Res 10: 37–38PubMedGoogle Scholar
  16. 16.
    Arriaga YL, Harville BA, Dreyfus LA (1995) Contribution of individual disulfide bonds to biological action of Escherichia coli heat-stable enterotoxin B. Infect Immun 63: 4715–4720PubMedGoogle Scholar
  17. 17.
    Labrie V, Harel J, Dubreuil JD (2001) Oligomerization of Escherichia coli enterotoxin b through its C-terminal hydrophobic α-helix Biochim Biophys Acta 1535: 128–133PubMedGoogle Scholar
  18. 18.
    Okamoto K, Baba T, Yamanaka H, Akashi N, Fujii Y (1995) Disulfide bond formation and secretion of Escherichia coli heat-stable enterotoxin II. J Bacteriol 177: 4579–4586PubMedGoogle Scholar
  19. 19.
    Rousset E, Harel J, Dubreuil JD (1998) Sulfatide from the pig jejunum brush border epithelial cell surface is involved in binding of Escherichia coli enterotoxin b. Infect Immun 66: 5650–5658PubMedGoogle Scholar
  20. 20.
    Kennedy DJ, Greenberg RN, Dunn JA, Abernathy R, Ryerse JS, Guerrant RL (1984) Effects of Escherichia coli heat-stable enterotoxin STb on intestines of mice, rats, rabbits, and piglets. Infect Immun 46: 639–643PubMedGoogle Scholar
  21. 21.
    Dreyfus LA, Harville B, Howard DE, Shaban R, Beatty DM, Morris SJ (1993) Calcium influx mediated by the Escherichia coli heat-stable enterotoxin B (STb). Proc Natl Acad Sci USA 90: 3202–3206PubMedCrossRefGoogle Scholar
  22. 22.
    Erume J, Berberov EM, Kachman SD, Scott MA, Zhou Y, Francis DH, Moxley RA (2008) Comparison of the contributions of heat-labile enterotoxin and heat-stable enterotoxin b to the virulence of enterotoxigenic Escherichia coli in F4ac receptor-positive young pigs. Infect Immun 76: 3141–3149PubMedCrossRefGoogle Scholar
  23. 23.
    Lucas ML, Duncan NW, O’Reilly NF, McIlvenny TJ, Nelson YB (2008) Lack of evidence in vivo for a remote effect of Escherichia coli heat stable enterotoxin on jejunal fluid absorption. Neurogastroenterol Motil 20: 532–538PubMedCrossRefGoogle Scholar
  24. 24.
    Gouaux E (1997) Channel-forming toxins: Tales of transformation. Curr Opin Struct Biol 7: 566–573PubMedCrossRefGoogle Scholar
  25. 25.
    Lesieur C, Vecsey-Semien B, Abrami L, Fivaz M, van der Goot FG (1997) Membrane insertion: The strategy of toxins. Mol Membr Biol 14: 45–64PubMedCrossRefGoogle Scholar
  26. 26.
    Kurisu G, Zakharov SD, Zhalnina MV, Bano S, Eroukova VY, Rokitskaya TI, Antonenko YN, Wiener MC, Cramer WA (2003) The structure of BtuB with bound colicin E3 R-domain implies a translocon. Nat Struct Biol 10: 948–954PubMedCrossRefGoogle Scholar
  27. 27.
    Yamashita E, Zhalnina MV, Zakharov SD, Sharma O, Cramer WA (2008) Crystal structures of the OmpF porin: Function in a colicin translocon. EMBO J 27: 2171–2180PubMedCrossRefGoogle Scholar
  28. 28.
    Choe S, Bennett MJ, Fujii G, Curmi PM, Kantardjieff KA, Collier RJ, Eisenberg D (1992) The crystal structure of diphtheria toxin. Nature 357: 216–222PubMedCrossRefGoogle Scholar
  29. 29.
    Ratts R, Zeng H, Berg EA, Blue C, McComb ME, Costello CE, van der Spek JC, Murphy JR (2003) The cytosolic entry of diphtheria toxin catalytic domain requires a host cell cytosolic translocation factor complex. J Cell Biol 160: 1139–1150PubMedCrossRefGoogle Scholar
  30. 30.
    Tilley SJ, Saibil HR (2006) The mechanism of pore formation by bacterial toxins. Curr Opin Struct Biol 16: 230–236PubMedCrossRefGoogle Scholar
  31. 31.
    Iacovache I, Paumard P, Scheib H, Lesieur C, Sakai N, Matile S, Parker MW, van der Goot FG (2006) A rivet model for channel formation by aerolysin-like pore-forming toxins. EMBO J 25: 457–466PubMedCrossRefGoogle Scholar
  32. 32.
    Nassi S, Collier RJ, Finkelstein A (2002) PA63 channel of anthrax toxin: An extended β-barrel. Biochemistry 41: 1445–1450PubMedCrossRefGoogle Scholar
  33. 33.
    Moniatte M, van der Goot FG, Buckley JT, Pattus F, van Dorsselaer A (1996) Characterisation of the heptameric pore-forming complex of the Aeromonas toxin aerolysin using MALDI-TOF mass spectrometry. FEBS Lett 384: 269–272PubMedCrossRefGoogle Scholar
  34. 34.
    Parker MW, Feil SC (2005) Pore-forming protein toxins: From structure to function. Prog Biophys Mol Biol 88: 91–142PubMedCrossRefGoogle Scholar
  35. 35.
    Sekiya K, Satoh R, Danbara H, Futaesaku Y (1993) A ring-shaped structure with a crown formed by streptolysin O on the erythrocyte membrane. J Bacteriol 175: 5953–5961PubMedGoogle Scholar
  36. 36.
    Park JM, Ng VH, Maeda S, Rest RF, Karin M (2004) Anthrolysin O and other gram-positive cytolysins are toll-like receptor 4 agonists. J Exp Med 200: 1647–1655PubMedCrossRefGoogle Scholar
  37. 37.
    Rosado CJ, Kondos S, Bull TE, Kuiper MJ, Law RH, Buckle AM, Voskoboinik I, Bird PI, Trapani JA, Whisstock JC, Dunstone MA (2008) The MACPF/CDC family of pore-forming toxins. Cell Microbiol 10: 1765–1774PubMedCrossRefGoogle Scholar
  38. 38.
    Rossjohn J, Polekhina G, Feil SC, Morton CJ, Tweten RK, Parker MW (2007) Structures of perfringolysin O suggest a pathway for activation of cholesterol-dependent cytolysins. J Mol Biol 367: 1227–1236PubMedCrossRefGoogle Scholar
  39. 39.
    Tweten RK (2005) Cholesterol-dependent cytolysins, a family of versatile pore-forming toxins. Infect Immun 73: 6199–6209PubMedCrossRefGoogle Scholar
  40. 40.
    Tweten RK (2005) Cholesterol-dependent cytolysins, a family of versatile pore-forming toxins. Infect Immun 73: 6199–6209PubMedCrossRefGoogle Scholar
  41. 41.
    Ramachandran R, Tweten RK, Johnson AE (2005) The domains of a cholesterol-dependent cytolysin undergo a major FRET-detected rearrangement during pore formation. Proc Natl Acad Sci USA 102: 7139–7144PubMedCrossRefGoogle Scholar
  42. 42.
    Rosado CJ, Kondos S, Bull TE, Kuiper MJ, Law RH, Buckle AM, Voskobolnlk I, Bird PI, Trapani JA, Whisstock JC, Dunstone MA (2008) The MACPF/CDC family of pore-forming toxins. Cell Microbiol 10: 1765–1774PubMedCrossRefGoogle Scholar
  43. 43.
    Tilley SJ, Orlova EV, Gilbert RJ, Andrew PW, Saibil HR (2005) Structural basis of pore formation by the bacterial toxin pneumolysin. Cell 121: 247–256PubMedCrossRefGoogle Scholar
  44. 44.
    Yoshino K, Abe J, Murata H, Takao T, Kohsaka T, Shimonishi Y, Takeda T (1994) Purification and characterization of a novel superantigen produced by a clinical isolate of Yersinia pseudotuberculosis. FEBS Lett 356: 141–144PubMedCrossRefGoogle Scholar
  45. 45.
    McCormick JK, Yarwood JM, Schlievert PM (2001) Toxic shock syndrome and bacterial superantigens: An update. Annu Rev Microbiol 55: 77–104PubMedCrossRefGoogle Scholar
  46. 46.
    Bergdoll MS (1983) Enterotoxins. In: CSF Easmon, C Adlam (eds): Staphylococci and Staphylococcal Infections. Academic Press, London, 559–598Google Scholar
  47. 47.
    Fraser JD, Proft T (2008) The bacterial superantigen and superantigen-like proteins. Immunol Rev 225: 226–243PubMedCrossRefGoogle Scholar
  48. 48.
    Donadini R, Liew CW, Kwan AH, Mackay JP, Fields BA (2004) Crystal and solution structures of a superantigen from Yersinia pseudotuberculosis reveal a jelly-roll fold. Structure 12: 145–156PubMedCrossRefGoogle Scholar
  49. 49.
    Al-Shangiti AM, Naylor CE, Nair SP, Briggs DC, Henderson B, Chain BM (2004) Structural relationships and cellular tropism of staphylococcal superantigen-like proteins. Infect Immun 72: 4261–4270PubMedCrossRefGoogle Scholar
  50. 50.
    Arcus VL, Langley R, Proft T, Fraser JD, Baker EN (2002) The three-dimensional structure of a superantigen-like protein, SET3, from a pathogenicity island of the Staphylococcus aureus genome. J Biol Chem 277: 32274–32281PubMedCrossRefGoogle Scholar
  51. 51.
    Chung MC, Wines BD, Baker H, Langley RJ, Baker EN, Fraser JD (2007) The crystal structure of staphylococcal superantigen-like protein 11 in complex with sialyl Lewis X reveals the mechanism for cell binding and immune inhibition. Mol Microbiol 66: 1342–1355PubMedCrossRefGoogle Scholar
  52. 52.
    Langley R, Wines B, Willoughby N, Basu I, Proft T, Fraser JD (2005) The staphylococcal superantigen-like protein 7 binds IgA and complement C5 and inhibits IgA-Fc α RI binding and serum killing of bacteria. J Immunol 174: 2926–2933PubMedGoogle Scholar
  53. 53.
    Kim J, Urban RG, Strominger JL, Wiley DC (1994) Toxic shock syndrome toxin-1 complexed with a class II major histocompatibility molecule. Science 266: 1870–1874PubMedCrossRefGoogle Scholar
  54. 54.
    Gunther S, Varma AK, Moza B, Kasper KJ, Wyatt AW, Zhu P, Rahman AK, Li Y, Mariuzza RA, McCormick JK, Sundberg EJ (2007) A novel loop domain in superantigens extends their T cell receptor recognition site. J Mol Biol 371: 210–221PubMedCrossRefGoogle Scholar
  55. 55.
    Li Y, Li H, Dimasi N, McCormick JK, Martin R, Schuck P, Schlievert PM, Mariuzza RA (2001) Crystal structure of a superantigen bound to the high-affinity, zinc-dependent site on MHC class II. Immunity 14: 93–104PubMedCrossRefGoogle Scholar
  56. 56.
    Zhao Y, Li Z, Drozd SJ, Guo Y, Mourad W, Li H (2004) Crystal structure of Mycoplasma arthritidis mitogen complexed with HLA-DR1 reveals a novel superantigen fold and a dimerized superantigen-MHC complex. Structure 12: 277–288PubMedGoogle Scholar
  57. 57.
    Sundberg EJ, Deng L, Mariuzza RA (2007) TCR recognition of peptide/MHC class II complexes and superantigens. Semin Immunol 19: 262–271PubMedCrossRefGoogle Scholar
  58. 58.
    Pless DD, Ruthel G, Reinke EK, Ulrich RG, Bavari S (2005) Persistence of zinc-binding bacterial superantigens at the surface of antigen-presenting cells contributes to the extreme potency of these superantigens as T-cell activators. Infect Immun 73: 5358–5366PubMedCrossRefGoogle Scholar
  59. 59.
    Sundberg EJ, Li H, Llera AS, McCormick JK, Tormo J, Schlievert PM, Karjalainen K, Mariuzza RA (2002) Structures of two streptococcal superantigens bound to TCR β chains reveal diversity in the architecture of T cell signaling complexes. Structure 10: 687–699PubMedCrossRefGoogle Scholar
  60. 60.
    Sundberg EJ, Deng L, Mariuzza RA (2007) TCR recognition of peptide/MHC class II complexes and superantigens. Semin Immunol 19: 262–271PubMedCrossRefGoogle Scholar
  61. 61.
    Yang X, Buonpane RA, Moza B, Rahman AK, Wang N, Schlievert PM, McCormick JK, Sundberg EJ, Kranz DM (2008) Neutralization of multiple staphylococcal superantigens by a single-chain protein consisting of affinity-matured, variable domain repeats. J Infect Dis 198: 344–348PubMedCrossRefGoogle Scholar
  62. 62.
    Thomas D, Dauwalder O, Brun V, Badiou C, Ferry T, Etienne J, Vandenesch F, Lina G (2009) Staphylococcus aureus superantigens elicit redundant and extensive human Vβ patterns. Infect Immun 77: 2043–2050PubMedCrossRefGoogle Scholar
  63. 63.
    Ostolaza H, Soloaga A, Goni FM (1995) The binding of divalent cations to Escherichia coli α-haemolysin. Eur J Biochem 228: 39–44PubMedGoogle Scholar
  64. 64.
    Wolff N, Ghigo JM, Delepelaire P, Wandersman C, Delepierre M (1994) C-terminal secretion signal of an Erwinia chrysanthemi protease secreted by a signal peptide-independent pathway: Proton NMR and CD conformational studies in membrane-mimetic environments. Biochemistry 33: 6792–6801PubMedCrossRefGoogle Scholar
  65. 65.
    Allenby NE, O’Connor N, Pragai Z, Carter NM, Miethke M, Engelmann S, Hecker M, Wipat A, Ward AC, Harwood CR (2004) Post-transcriptional regulation of the Bacillus subtilis pst operon encoding a phosphate-specific ABC transporter. Microbiology 150: 2619–2628PubMedCrossRefGoogle Scholar
  66. 66.
    Delepelaire P (2004) Type I secretion in gram-negative bacteria. Biochim Biophys Acta 1694: 149–161PubMedCrossRefGoogle Scholar
  67. 67.
    Letoffe S, Delepelaire P, Wandersman C (1996) Protein secretion in gram-negative bacteria: Assembly of the three components of ABC protein-mediated exporters is ordered and promoted by substrate binding. EMBO J 15: 5804–5811PubMedGoogle Scholar
  68. 68.
    Glaser P, Danchin A, Ladant D, Barzu O, Ullmann A (1988) Bordetella pertussis adenylate cyclase: The gene and the protein. Tokai J Exp Clin Med 13 Suppl: 239–252PubMedGoogle Scholar
  69. 69.
    Guermonprez P, Khelef N, Blouin E, Rieu P, Ricciardi-Castagnoli P, Guiso N, Ladant D, Leclerc C (2001) The adenylate cyclase toxin of Bordetella pertussis binds to target cells via the α(M)β(2) integrin (CD11b/CD18). J Exp Med 193: 1035–1044PubMedCrossRefGoogle Scholar
  70. 70.
    Weingart CL, Mobberley-Schuman, PS, Hewlett, EL, Gray, MC, Weiss AA (2000) Neutralizing antibodies to andenylate cyclase toxin promote phagocytosis of Bordetella pertussis by human neutrophils. Infect Immun 68: 7152–7155PubMedCrossRefGoogle Scholar
  71. 71.
    Rogel A, Hanski E (1992) Distinct steps in the penetration of adenylate cyclase toxin of Bordetella pertussis into sheep erythrocytes. Translocation of the toxin across the membrane. J Biol Chem 267: 22599–22605PubMedGoogle Scholar
  72. 72.
    Cheung GY, Kelly SM, Jess TJ, Prior S, Price NC, Parton R, Coote JG (2009) Functional and structural studies on different forms of the adenylate cyclase toxin of Bordetella pertussis. Microb Pathog 46: 36–42PubMedCrossRefGoogle Scholar
  73. 73.
    Arnoff DM, Canetti C, Serezani CH, Luo M, Peters-Golden M (2005) Cutting edge: Macrophage inhibition by cyclic AMP (cAMP): Differential roles of protein kinase A and exchange protein directly activated by cAMP-1. J Immunol 174: 595–599Google Scholar
  74. 74.
    Galgani M, De Rosa V, De Simone S, Leonardi A, D’Oro U, Napolitani G, Masci AM, Zappacosta S, Racioppi L (2004) Cyclic AMP modulates the functional plasticity of immature dendritic cells by inhibiting Src-like kinases through protein kinase A-mediated signaling. J Biol Chem 279: 32507–32514PubMedCrossRefGoogle Scholar
  75. 75.
    Ehrmann IE, Gray MC, Gordon VM, Gray LS, Hewlett EL (1991) Hemolytic activity of adenylate cyclase toxin from Bordetella pertussis. FEBS Lett 278: 79–83PubMedCrossRefGoogle Scholar
  76. 76.
    Chenal A, Guijarro JI, Raynal B, Delepierre M, Ladant D (2009) RTX calcium binding motifs are intrinsically disordered in the absence of calcium: Implication for protein secretion. J Biol Chem 284: 1781–1789PubMedCrossRefGoogle Scholar
  77. 77.
    Kamanova J, Kofronova O, Masin J, Genth H, Vojtova J, Linhartova I, Benada O, Just I, Sebo P (2008) Adenylate cyclase toxin subverts phagocyte function by RhoA inhibition and unproductive ruffling. J Immunol 181: 5587–5597PubMedGoogle Scholar
  78. 78.
    Watanabe M, Blobel G (1989) SecB functions as a cytosolic signal recognition factor for protein export in E. coli. Cell 58: 695–705PubMedCrossRefGoogle Scholar
  79. 79.
    Johnson TL, Abendroth J, Hol WG, Sandkvist M (2006) Type II secretion: From structure to function. FEMS Microbiol Lett 255: 175–186PubMedCrossRefGoogle Scholar
  80. 80.
    Henderson IR, Navarro-Garcia F, Desvaux M, Fernandez RC, Ala’Aldeen D (2004) Type V protein secretion pathway: The autotransporter story. Microbiol Mol Biol Rev 68: 692–744PubMedCrossRefGoogle Scholar
  81. 81.
    Martoglio B, Dobberstein B (1998) Signal sequences: More than just greasy peptides. Trends Cell Biol 8: 410–415PubMedCrossRefGoogle Scholar
  82. 82.
    Yanez ME, Korotkov KV, Abendroth J, Hol WG (2008) Structure of the minor pseudopilin EpsH from the Type 2 secretion system of Vibrio cholerae. J Mol Biol 377: 91–103PubMedCrossRefGoogle Scholar
  83. 83.
    Bachert C, Zhang N, Patou J, van Zele T, Gevaert P (2008) Role of staphylococcal superantigens in upper airway disease. Curr Opin Allergy Clin Immunol 8: 34–38PubMedCrossRefGoogle Scholar
  84. 84.
    Van Heyningen S (1974) Cholera toxin: Interaction of subunits with ganglioside GMI. Science 183: 656–657CrossRefGoogle Scholar
  85. 85.
    Chinnapen DJ, Chinnapen H, Saslowsky D, Lencer WI (2007) Rafting with cholera toxin: Endocytosis and trafficking from plasma membrane to ER. FEMS Microbiol Lett 266: 129–137PubMedCrossRefGoogle Scholar
  86. 86.
    Rodighiero C, Tsai B, Rapoport TA, Lencer WI (2002) Role of ubiquitination in retro-translocation of cholera toxin and escape of cytosolic degradation. EMBO Rep 3: 1222–1227PubMedCrossRefGoogle Scholar
  87. 87.
    Moss J, Manganiello VC, Vaughan M (1976) Hydrolysis of nicotinamide adenine dinucleotide by choleragen and its A protomer: Possible role in the activation of adenylate cyclase. Proc Natl Acad Sci USA 73: 4424–4427PubMedCrossRefGoogle Scholar
  88. 88.
    Gill DM (1975) Involvement of nicotinamide adenine dinucleotide in the action of cholera toxin in vitro. Proc Natl Acad Sci USA 72: 2064–2068PubMedCrossRefGoogle Scholar
  89. 89.
    Cheng SH, Rich DP, Marshall J, Gregory RJ, Welsh MJ, Smith AE (1991) Phosphorylation of the R domain by cAMP-dependent protein kinase regulates the CFTR chloride channel. Cell 66: 1027–1036PubMedCrossRefGoogle Scholar
  90. 90.
    Halm DR, Rechkemmer GR, Schoumacher RA, Frizzell RA (1988) Apical membrane chloride channels in a colonic cell line activated by secretory agonists. Am J Physiol 254: C505–511PubMedGoogle Scholar
  91. 91.
    Nystrom-Asklin J, Adamsson J, Harandi AM (2008) The adjuvant effect of CpG oligodeoxynucleotide linked to the non-toxic B subunit of cholera toxin for induction of immunity against H. pylori in mice. Scand J Immunol 67: 431–440PubMedCrossRefGoogle Scholar
  92. 92.
    Plano GV, Day JB, Ferracci F (2001) Type III export: New uses for an old pathway. Mol Microbiol 40: 284–293PubMedCrossRefGoogle Scholar
  93. 93.
    Marlovits TC, Kubori T, Sukhan A, Thomas DR, Galan JE, Unger VM (2004) Structural insights into the assembly of the type III secretion needle complex. Science 306: 1040–1042PubMedCrossRefGoogle Scholar
  94. 94.
    Kenjale R, Wilson J, Zenk SF, Saurya S, Picking WL, Picking WD, Blocker A (2005) The needle component of the type III secreton of Shigella regulates the activity of the secretion apparatus. J Biol Chem 280: 42929–42937PubMedCrossRefGoogle Scholar
  95. 95.
    Veenendaal AK, Hodgkinson JL, Schwarzer L, Stabat D, Zenk SF, Blocker AJ (2007) The type III secretion system needle tip complex mediates host cell sensing and translocon insertion. Mol Microbiol 63: 1719–1730PubMedCrossRefGoogle Scholar
  96. 96.
    Picking WL, Nishioka H, Hearn PD, Baxter MA, Harrington AT, Blocker A, Picking WD (2005) IpaD of Shigella flexneri is independently required for regulation of Ipa protein secretion and efficient insertion of IpaB and IpaC into host membranes. Infect Immun 73: 1432–1440PubMedCrossRefGoogle Scholar
  97. 97.
    Goehring UM, Schmidt G, Pederson KJ, Aktories K, Barbieri JT (1999) The N-terminal domain of Pseudomonas aeruginosa exoenzyme S is a GTPase-activating protein for Rho GTPases. J Biol Chem 274: 36369–36372PubMedCrossRefGoogle Scholar
  98. 98.
    Krall R, Sun J, Pederson KJ, Barbieri JT (2002) In vivo rho GTPase-activating protein activity of Pseudomonas aeruginosa cytotoxin ExoS. Infect Immun 70: 360–367PubMedCrossRefGoogle Scholar
  99. 99.
    Wurtele M, Wolf E, Pederson KJ, Buchwald G, Ahmadian MR, Barbieri JT, Wittinghofer A (2001) How the Pseudomonas aeruginosa ExoS toxin downregulates Rac. Nat Struct Biol 8: 23–26PubMedCrossRefGoogle Scholar
  100. 100.
    Ganesan AK, Vincent TS, Olson JC, Barbieri JT (1999) Pseudomonas aeruginosa exoenzyme S disrupts Ras-mediated signal transduction by inhibiting guanine nucleotide exchange factor-catalyzed nucleotide exchange. J Biol Chem 274: 21823–21829PubMedCrossRefGoogle Scholar
  101. 101.
    Deng Q, Barbieri JT (2008) Modulation of host cell endocytosis by the type III cytotoxin, Pseudomonas ExoS. Traffic 9: 1948–1957PubMedCrossRefGoogle Scholar
  102. 102.
    Maresso AW, Deng Q, Pereckas MS, Wakim BT, Barbieri JT (2007) Pseudomonas aeruginosa ExoS ADP-ribosyltransferase inhibits ERM phosphorylation. Cell Microbiol 9: 97–105PubMedCrossRefGoogle Scholar
  103. 103.
    Fu H, Coburn J, Collier RJ (1993) The eukaryotic host factor that activates exoenzyme S of Pseudomonas aeruginosa is a member of the 14-3-3 protein family. Proc Natl Acad Sci USA 90: 2320–2324PubMedCrossRefGoogle Scholar
  104. 104.
    Zhang Y, Barbieri JT (2005) A leucine-rich motif targets Pseudomonas aeruginosa ExoS within mammalian cells. Infect Immun 73: 7938–7945PubMedCrossRefGoogle Scholar
  105. 105.
    Roy-Burman A, Savel RH, Racine S, Swanson BL, Revadigar NS, Fujimoto J, Sawa T, Frank DW, Wiener-Kronish JP (2001) Type III protein secretion is associated with death in lower respiratory and systemic Pseudomonas aeruginosa infections. J Infect Dis 183: 1767–1774PubMedCrossRefGoogle Scholar
  106. 106.
    Corech R, Rao A, Laxova A, Moss J, Rock MJ, Li Z, Kosorok MR, Splaingard ML, Farrell PM, Barbieri JT (2005) Early immune response to the components of the type III system of Pseudomonas aeruginosa in children with cystic fibrosis. J Clin Microbiol 43: 3956–3962PubMedCrossRefGoogle Scholar
  107. 107.
    Burns DL (2003) Type IV transporters of pathogenic bacteria. Curr Opin Microbiol 6: 29–34PubMedCrossRefGoogle Scholar
  108. 108.
    Christie PJ, Atmakuri K, Krishnamoorthy V, Jakubowski S, Cascales E (2005) Biogenesis, architecture, and function of bacterial type IV secretion systems. Annu Rev Microbiol 59: 451–485PubMedCrossRefGoogle Scholar
  109. 109.
    Saier MH (2006) Protein secretion and membrane insertion systems in Gram-negative bacteria. J Membr Biol 214: 75–90PubMedCrossRefGoogle Scholar
  110. 110.
    Planet PJ, Kachlany SC, DeSalle R, Figurski DH (2001) Phylogeny of genese for secretion NTPases: Identification of the widespread tadA subfamily and development of a diagnostic key for gene classification. Proc Natl Acad Sci USA 98: 2503–2508PubMedCrossRefGoogle Scholar
  111. 111.
    Savvides SN, Yeo HJ, Beck MR, Blaesing F, Lurz R, Lanka E, Buhrdorf R, Fischer W, Haas R, Waksman G (2003) VirB11 ATPases are dynamic hexameric assemblies: New insights into bacterial type IV secretion. EMBO J 22: 1969–1980PubMedCrossRefGoogle Scholar
  112. 112.
    Fronzes R, Schafer E, Wang L, Saibil HR, Orlova EV, Waksman G (2009) Structure of a type IV secretion system core complex. Science 323: 266–268PubMedCrossRefGoogle Scholar
  113. 113.
    Backert S, Meyer TF (2006) Type IV secretion systems and their effectors in bacterial pathogenesis. Curr Opin Microbiol 9: 207–217PubMedCrossRefGoogle Scholar
  114. 114.
    De Felipe KS, Glover RT, Charpentier X, Anderson OR, Reyes M, Pericone CD, Shuman HA (2008) Legionella eukaryotic-like type IV substrates interfere with organelle trafficking. PLoS Pathog 4: e1000117PubMedCrossRefGoogle Scholar
  115. 115.
    Ragaz C, Pietsch H, Urwyler S, Tiaden A, Weber SS, Hilbi H (2008) The Legionella pneumophila phosphatidylinositol-4 phosphate-binding type IV substrate SidC recruits endoplasmic reticulum vesicles to a replication-permissive vacuole. Cell Microbiol 10: 2416–2433PubMedCrossRefGoogle Scholar
  116. 116.
    Henderson IR, Navarro-Garcia F, Desvaux M, Fernandez RC, Ala’Aldeen D (2004) Type V protein secretion pathway: The autotransporter story. Microbiol Mol Biol Rev 68: 692–744PubMedCrossRefGoogle Scholar
  117. 117.
    Henderson IR, Navarro-Garcia F, Nataro JP (1998) The great escape: Structure and function of the autotransporter proteins. Trends Microbiol 6: 370–378PubMedCrossRefGoogle Scholar
  118. 118.
    Loveless BJ, Saier MH (1997) A novel family of channel-forming, autotransporting, bacterial virulence factors. Mol Membr Biol 14: 801–807CrossRefGoogle Scholar
  119. 119.
    Yen MR, Peabody CR, Partovi SM, Zhai Y, Tseng YH, Saier MH (2002) Protein-translocating outer membrane porins of Gram-negative bacteria. Biochim Biophys Acta 1562: 6–31PubMedCrossRefGoogle Scholar
  120. 120.
    Oliver DC, Huang G, Nodel E, Pleasance S, Fernandez RC (2003) A conserved region within the Bordetella pertussis autotransporter BrkA is necessary for folding of its passenger domain. Mol Microbiol 47: 1367–1383PubMedCrossRefGoogle Scholar
  121. 121.
    Brunder W, Schmidt H, Karch H (1997) EspP, a novel extracellular serine protease of enterohaemorrhagic Escherichia coli O157:H7 cleaves human coagulation factor V. Mol Microbiol 24: 767–778PubMedCrossRefGoogle Scholar
  122. 122.
    Leininger E, Roberts M, Kenimer JG, Charles IG, Fairweather N, Novotny P, Brennan MJ (1991) Pertactin, an Arg-Gly-Asp-containing Bordetella pertussis surface protein that promotes adherence of mammalian cells. Proc Natl Acad Sci USA 88: 345–349PubMedCrossRefGoogle Scholar
  123. 123.
    St Geme JW, Cutter D (2000) The Haemophilus influenzae Hia adhesin is an autotransporter protein that remains uncleaved at the C terminus and fully cell associated. J. Bacteriol 182: 6005–6013PubMedCrossRefGoogle Scholar
  124. 124.
    Henderson IR, Cappello R, Nataro JP (2000) Autotransporter proteins evolution and redefining protein secretion. Trends Microbiol 8: 529–532PubMedCrossRefGoogle Scholar
  125. 125.
    Jacob-Dubuisson F, Locht C, Antoine R (2001) Two-partner secretion in Gram-negative bacteria: A thrifty, specific pathway for large virulence proteins. Mol Microbiol 40: 306–313PubMedCrossRefGoogle Scholar
  126. 126.
    Grass S, St Geme JW (2000) Maturation and secretion of the non-typable Haemophilus influenzae HMW1 adhesin: Roles of the N-terminal and C-terminal domains. Mol Microbiol 36: 55–67PubMedCrossRefGoogle Scholar
  127. 127.
    Guedin S, Willery E, Tommassen J, Fort E, Drobecq H, Locht C, Jacob-Dubuisson F (2000) Novel topological features of FhaC, the outer membrane transporter involved in the secretion of the Bordetella pertussis filamentous hemagglutinin. J Biol Chem 275: 30202–30210PubMedCrossRefGoogle Scholar
  128. 128.
    Jacob-Dubuisson F, Buisine C, Willery E, Renauld-Mongenie G, Locht C (1997) Lack of functional complementation between Bordetella pertussis filamentous hemagglutinin and Proteus mirabilis HpmA hemolysin secretion machineries. J Bacteriol 179: 775–783PubMedGoogle Scholar
  129. 129.
    Klauser T, Pohlner J, Meyer TF (1993) The secretion pathway of IgA protease-type proteins in gram-negative bacteria. Bioessays 15: 799–805PubMedCrossRefGoogle Scholar
  130. 130.
    Frangione B, Franklin EC (1972) Chemical typing of the immunoglobulins IgM, IgA1 and IgA2. FEBS Lett 20: 321–323PubMedCrossRefGoogle Scholar
  131. 131.
    Pukatzki S, Ma AT, Sturtevant D, Krastins B, Sarracino D, Nelson WC, Heidelberg JF, Mekalanos JJ (2006) Identification of a conserved bacterial protein secretion system in Vibrio cholerae using the Dictyostelium host model system. Proc Natl Acad Sci USA 103: 1528–1533PubMedCrossRefGoogle Scholar
  132. 132.
    Mougous JD, Cuff ME, Raunser S, Shen A, Zhou M, Gifford CA, Goodman AL, Joachimiak G, Ordonez CL, Lory S, Walz T, Joachimiak A, Mekalanos JJ (2006) A virulence locus of Pseudomonas aeruginosa encodes a protein secretion apparatus. Science 312: 1526–1530PubMedCrossRefGoogle Scholar
  133. 133.
    Abdallah AM, Gey van Pittius NC, Champion PA, Cox J, Luirink J, Vandenbroucke-Grauls CM, Appelmelk BJ, Bitter W (2007) Type VII secretion-Mycobacteria show the way. Nat Rev Microbiol 5: 883–891PubMedCrossRefGoogle Scholar
  134. 134.
    Schiavo G, Rossetto O, Santucci A, DasGupta BR, Montecucco C (1992) Botulinum neurotoxins are zink proteins. J Biol Chem 267: 23479–23483PubMedGoogle Scholar
  135. 135.
    Tanzi MG, Gabay MP (2002) Association between honey consumption and infant botulism. Pharmacotherapy 22: 1479–1483PubMedCrossRefGoogle Scholar
  136. 136.
    Dastoor SF, Misch CE, Wang HL (2007) Botulinum toxin (Botox) to enhance facial macroesthetics: A literature review. J Oral Implantol 33: 164–171PubMedCrossRefGoogle Scholar
  137. 137.
    Callaway JE (2004) Botulinum toxin type B (Myobloc): Pharmacology and biochemistry. Clin Dermatol 22: 23–28PubMedCrossRefGoogle Scholar
  138. 138.
    Dressler D, Munchau A, Bhatia KP, Quinn NP, Bigalke H (2002) Antibody-induced botulinum toxin therapy failure: Can it be overcome by increased botulinum toxin doses? Eur Neurol 47: 118–121PubMedCrossRefGoogle Scholar
  139. 139.
    Dressler D, Bigalke H (2002) Botulinum toxin antibody type A titres after cessation of botulinum toxin therapy. Mov Disord 17: 170–173PubMedCrossRefGoogle Scholar
  140. 140.
    Suen JC, Hatheway CL, Steigerwalt AG, Brenner DJ (1988) Genetic confirmation of identities of neurotoxigenic Clostridium baratii and Clostridium butyricum implicated as agents of infant botulism. J Clin Microbiol 26: 2191–2192PubMedGoogle Scholar
  141. 141.
    Popoff MR, Marvaud JC (1999) Structural and genomic features of clostridial neurotoxins. In: JE Alouf, JH Freer (eds). The Comprehensive Sourcebook of Bacterial Protein Toxins. Academic Press, London, 174–201Google Scholar
  142. 142.
    Dineen SS, Bradshaw M, Karasek CE, Johnson EA (2004) Nucleotide sequence and transcriptional analysis of the type A2 neurotoxin gene cluster in Clostridium botulinum. FEMS Microbiol Lett 235: 9–16PubMedCrossRefGoogle Scholar
  143. 143.
    Oguma K, Inoue K, Fujinaga Y, Yokota K, Watanabe T, Ohyama T, Takeshi K, Inoue K (1999) Structure and function of Clostridium botulinum progenitor toxin. J Toxicol Toxin Rev 18: 17–34Google Scholar
  144. 144.
    Quinn CP, Minton NP (2001) Clostridial neurotoxins. In: H Bahl, P Dürre (eds): Clostridia. Biotechnology and Medical Applications. Wiley-VCH, Weinheim, 211–250Google Scholar
  145. 145.
    Sharma SK, Ramzan MA, Singh BR (2003) Separation of the components of type A botulinum neurotoxin complex by electrophoresis. Toxicon 41: 321–331PubMedCrossRefGoogle Scholar
  146. 146.
    Rodriguez Jovita M, Collins MD, East AK (1998) Gene organization and sequence determination of the two botulinum neurotoxin gene clusters in Clostridium botulinum type A(B) strain NCTC 2916. Curr Microbiol 36: 226–231PubMedCrossRefGoogle Scholar
  147. 147.
    East AK, Richardson PT, Allaway D, Collins MD, Roberts TA, Thompson DE (1992) Sequence of the gene encoding type F neurotoxin of Clostridium botulinum. FEMS Microbiol Lett 75: 225–230PubMedCrossRefGoogle Scholar
  148. 148.
    Sugii S, Ohishi I, Sakaguchi G (1977) Correlation between oral toxicity and in vitro stability of Clostridium botulinum type A and B toxins of different molecular sizes. Infect Immun 16: 910–914PubMedGoogle Scholar
  149. 149.
    Bandyopadhyay S, Clark AW, DasGupta BR, Sathyamoorthy V (1987) Role of the heavy and light chains of botulinum neurotoxin in neuromuscular paralysis. J Biol Chem 262: 2660–2663PubMedGoogle Scholar
  150. 150.
    Couesnon A, Pereira Y, Popoff MR (2007) Receptor-mediated transcytosis of botulinum neurotoxin A through intestinal cell monolayers. Cell Microbiol 10: 375–387PubMedGoogle Scholar
  151. 151.
    Jin Y, Takegahara Y, Sugawara Y, Matsumura T, Fujinaga Y (2009) Disruption of the epithelial barrier by botulinum haemagglutinin (HA) proteins-Differences in cell tropism and the mechanism of action between HA proteins of types A or B, and HA proteins of type C. Microbiology 155: 35–45PubMedCrossRefGoogle Scholar
  152. 152.
    Maksymowych AB, Simpson LL (1998) Binding and transcytosis of botulinum neurotoxin by polarized human colon carcinoma cells. J Biol Chem 273: 21950–21957PubMedCrossRefGoogle Scholar
  153. 153.
    Park JB, Simpson LL (2003) Inhalational poisoning by botulinum toxin and inhalation vaccination with its heavy-chain component. Infect Immun 71: 1147–1154PubMedCrossRefGoogle Scholar
  154. 154.
    Couesnon A, Pereira Y, Popoff MR (2008) Receptor-mediated transcytosis of botulinum neurotoxin A through intestinal cell monolayers. Cell Microbiol 10: 375–387PubMedGoogle Scholar
  155. 155.
    Couesnon A, Shimizu T, Popoff MR (2009) Differential entry of botulinum neurotoxin A into neuronal and intestinal cells. Cell Microbiol 11: 289–308PubMedCrossRefGoogle Scholar
  156. 156.
    Kitamura M, Takamiya K, Aizawa S, Furukawa K (1999) Gangliosides are the binding substances in neural cells for tetanus and botulinum toxins in mice. Biochim Biophys Acta 1441: 1–3PubMedGoogle Scholar
  157. 157.
    Dong M, Yeh F, Tepp WH, Dean C, Johnson EA, Janz R, Chapman ER (2006) SV2 is the protein receptor for botulinum neurotoxin A. Science 312: 592–596PubMedCrossRefGoogle Scholar
  158. 158.
    Dong M, Liu H, Tepp WH, Johnson EA, Janz R, Chapman ER (2008) Glycosylated SV2A and SV2B mediate the entry of botulinum neurotoxin E into neurons. Mol Biol Cell 19: 5226–5237PubMedCrossRefGoogle Scholar
  159. 159.
    Rummel A, Karnath T, Henke T, Bigalke H, Binz T (2004) Synaptotagmins I and II act as nerve cell receptors for botulinum neurotoxin G. J Biol Chem 279: 30865–30870PubMedCrossRefGoogle Scholar
  160. 160.
    Dong M, Richards DA, Goodnough MC, Tepp WH, Johnson EA, Chapman ER (2003) Synaptotagmins I and II mediate entry of botulinum neurotoxin B into cells. J Cell Biol 162: 1293–1303PubMedCrossRefGoogle Scholar
  161. 161.
    Tsukamoto K, Kohda T, Mukamoto M, Takeuchi K, Ihara H, Saito M, Kozaki S (2005) Binding of Clostridium botulinum type C and D neurotoxins to ganglioside and phospholipid. Novel insights into the receptor for clostridial neurotoxins. J Biol Chem 280: 35164–35171PubMedCrossRefGoogle Scholar
  162. 162.
    Rummel A, Bade S, Alves J, Bigalke H, Binz T (2003) Two carbohydrate binding sites in the H(CC)-domain of tetanus neurotoxin are required for toxicity. J Mol Biol 326: 835–847PubMedCrossRefGoogle Scholar
  163. 163.
    Yowler BC, Schengrund CL (2004) Botulinum neurotoxin A changes conformation upon binding to ganglioside GT1b. Biochemistry 43: 9725–9731PubMedCrossRefGoogle Scholar
  164. 164.
    Muraro L, Tosatto S, Motterlini L, Rossetto O, Montecucco C (2009) The N-terminal half of the receptor domain of botulinum neurotoxin A binds to microdomains of the plasma membrane. Biochem Biophys Res Commun 380: 76–80PubMedCrossRefGoogle Scholar
  165. 165.
    Jung N, Haucke V (2007) Clathrin-mediated endocytosis at synapses. Traffic 8: 1129–1136PubMedCrossRefGoogle Scholar
  166. 166.
    Morgans CW, Kensel-Hammes P, Hurley JB, Burton K, Idzerda R, McKnight GS, Bajjalieh SM (2009) Loss of the synaptic vesicle protein SV2B results in reduced neurotransmission and altered synaptic vesicle protein expression in the retina. PLoS ONE 4: e5230PubMedCrossRefGoogle Scholar
  167. 167.
    Baldwin MR, Barbieri JT (2009) Association of botulinum neurotoxins with synaptic vesicle protein complexes. Toxicon 54: 570–574PubMedCrossRefGoogle Scholar
  168. 168.
    Fischer A, Mushrush DJ, Lacy DB, Montal M (2008) Botulinum neurotoxin devoid of receptor binding domain translocates active protease. PLoS Pathog 4Google Scholar
  169. 169.
    Wang J, Meng J, Lawrence GW, Zurawski TH, Sasse A, Bodeker MO, Gilmore MA, Fernandez-Salas E, Francis J, Steward LE, Aoki KR, Dolly JO (2008) Novel chimeras of botulinum neurotoxins A and E unveil contributions from the binding, translocation, and protease domains to their functional characteristics. J Biol Chem 283: 16993–17002PubMedCrossRefGoogle Scholar
  170. 170.
    Fischer A, Montal M (2007) Single molecule detection of intermediates during botulinum neurotoxin translocation across membranes. Proc Natl Acad Sci USA 104: 10447–10452PubMedCrossRefGoogle Scholar
  171. 171.
    Montal M (2008) Translocation of botulinum neurotoxin light chain protease by the heavy chain protein-conducting channel. Taxicon 54: 565–569CrossRefGoogle Scholar
  172. 172.
    Lacy DB, Stevens RC (1999) Sequence homology and structural analysis of the clostridial neurotoxins. J Mol Biol 291: 1091–1104PubMedCrossRefGoogle Scholar
  173. 173.
    Binz T, Blasi J, Yamasaki S, Baumeister A, Link E, Südhof TC, Jahn R, Niemann H (1994) Proteolysis of SNAP-25 by types E and A botulinal neurotoxins. J Biol Chem 269: 1617–1620PubMedGoogle Scholar
  174. 174.
    Foran P, Lawrence GW, Shone CC, Foster KA, Dolly JO (1996) Botulinum neurotoxin C1 cleaves both syntaxin and SNAP-25 in intact and permeabilized chromaffin cells: Correlation with its blockade of catecholamine release. Biochemistry 35: 2630–2636PubMedCrossRefGoogle Scholar
  175. 175.
    Schiavo G, Shone CC, Bennett MK, Scheller RH, Montecucco C (1995) Botulinum neurotoxin type C cleaves a single Lys-Ala bond within the carboxyl-terminal region of syntaxins. J Biol Chem 270: 10566–10570PubMedCrossRefGoogle Scholar
  176. 176.
    Arndt JW, Yu W, Bi F, Stevens RC (2005) Crystal structure of botulinum neurotoxin type G light chain: Serotype divergence in substrate recognition. Biochemistry 44: 9574–9580PubMedCrossRefGoogle Scholar
  177. 177.
    Chen S, Hall C, Barbieri JT (2008) Substrate recognition of VAMP-2 by botulinum neurotoxin B and tetanus neurotoxin. J Biol Chem 283: 21153–21159PubMedCrossRefGoogle Scholar
  178. 178.
    Ahmed SA OM, Ludivico ML, Gilsdorf J, Smith LA (2008) Identification of residues surrounding the active site of type A botulinum neurotoxin important for substrate recognition and catalytic activity. Protein J 27: 151–162PubMedCrossRefGoogle Scholar
  179. 179.
    Chen S, Barbieri JT (2006) Unique substrate recognition by botulinum neurotoxins serotypes A and E. J Biol Chem 281: 10906–10911PubMedCrossRefGoogle Scholar
  180. 180.
    Chen S, Kim JP, Barbieri JT (2007) Mechanism of substrate recognition by botulinum neurotoxin serotype A. J Biol Chem 282: 9621–9627PubMedCrossRefGoogle Scholar
  181. 181.
    Rigoni M, Caccin P, Johnson EA, Montecucco C, Rossetto O (2001) Site-directed mutagenesis identifies active-site residues of the light chain of botulinum neurotoxin type A. Biochem Biophys Res Commun 288: 1231–1237PubMedCrossRefGoogle Scholar
  182. 182.
    Schmidt JJ, Stafford RG (2005) Botulinum neurotoxin serotype F: Identification of substrate recognition requirements and development of inhibitors with low nanomolar affinity. Biochemistry 44: 4067–4073PubMedCrossRefGoogle Scholar
  183. 183.
    Sikorra S, Henke T, Swaminathan S, Galli T, Binz T (2006) Identification of the amino acid residues rendering TI-VAMP insensitive toward botulinum neurotoxin B. J Mol Biol 357: 574–582PubMedCrossRefGoogle Scholar
  184. 184.
    Arndt JW, Chai Q, Christian T, Stevens R (2006) Structure of botulinum neurotoxin type D light chain at 1.65 A resolution: Repercussions for VAMP-2 substrate specificity. Biochemistry 45: 3255–3262PubMedCrossRefGoogle Scholar
  185. 185.
    Breidenbach MA, Brunger AT (2004) Substrate recognition strategy for botulinum neurotoxin serotype A. Nature 432: 925–929PubMedCrossRefGoogle Scholar
  186. 186.
    Chen S, Kim JJ, Barbieri JT (2007) Mechanism of substrate recognition by botulinum neurotoxin serotype A. J Biol Chem 282: 9621–9627PubMedCrossRefGoogle Scholar
  187. 187.
    Smith TJ, Lou J, Geren IN, Forsyth CM, Tsai R, LaPorte SL, Tepp WH, Bradshaw M, Johnson EA, Smith LA, Marks JD (2005) Sequence variation within botulinum neurotoxin serotypes impacts antibody binding and neutralization. Infect Immun 73: 5450–5457PubMedCrossRefGoogle Scholar
  188. 188.
    Arndt JW, Jacobson MJ, Abola EE, Forsyth CM, Tepp WH, Marks JD, Johnson EA, Stevens RC (2006) A structural perspective of the sequence variability within botulinum neurotoxin subtypes A1–A4. J Mol Biol 362: 733–742PubMedCrossRefGoogle Scholar
  189. 189.
    Hill KK, Smith TJ, Helma CH, Ticknor LO, Foley BT, Svensson RT, Brown JL, Johnson EA, Smith LA, Okinaka RT, Jackson PJ, Marks JD (2007) Genetic diversity among botulinum neurotoxin-producing clostridial strains. J Bacteriol 189: 818–832PubMedCrossRefGoogle Scholar
  190. 190.
    Edmond BJ, Guerra FA, Blake J, Hempler S (1977) Case of infant botulism in Texas. Tex Med 73: 85–88PubMedGoogle Scholar
  191. 191.
    Leighton GR (1923) Report to the Scottish Board of Health H.M. Stationery Office, LondonGoogle Scholar
  192. 192.
    Henkel JS, Jacobson M, Tepp W, Pier C, Johnson EA, Barbieri JT (2009) Catalytic properties of botulinum neurotoxin subtypes A3 and A4 (dagger). Biochemistry 48: 2522–2528PubMedCrossRefGoogle Scholar
  193. 193.
    Baldwin MR, Tepp WH, Przedpelski A, Pier CL, Bradshaw M, Johnson EA, Barbieri JT (2008) Subunit vaccine against the seven serotypes of botulism. Infect Immun 76: 1314–1318PubMedCrossRefGoogle Scholar
  194. 194.
    Schiavo G, Benfenati F, Poulain B, Rossetto O, Polverino de Laureto P, DasGupta BR, Montecucco C (1992) Tetanus and botulinum-B neurotoxins block neurotransmitter release by proteolytic cleavage of synaptobrevin. Nature 359: 832–835PubMedCrossRefGoogle Scholar
  195. 195.
    Schiavo G, Shone CC, Bennett MK, Scheller RH, Montecucco C (1995) Botulinum neurotoxin type C cleaves a single Lys-Ala bond within the carboxyl-terminal region of syntaxins. J Biol Chem 270: 10566–10570PubMedCrossRefGoogle Scholar
  196. 196.
    Williamson LC, Halpern JL, Montecucco C, Brown JE, Neale EA (1996) Clostridial neurotoxins and substrate proteolysis in intact neurons: Botulinum neurotoxin C acts on synaptosomal-associated protein of 25 kDa. J Biol Chem 271: 7694–7699PubMedCrossRefGoogle Scholar
  197. 197.
    Schiavo G, Rossetto O, Catsicas S, Polverino de Laureto P, DasGupta BR, Benfenati F, Montecucco C (1993) Identification of the nerve terminal targets of botulinum neurotoxin serotypes A, D, and E. J Biol Chem 268: 23784–23787PubMedGoogle Scholar
  198. 198.
    Schiavo G, Shone CC, Rossetto O, Alexander FC, Montecucco C (1993) Botulinum neurotoxin serotype F is a zinc endopeptidase specific for VAMP/synaptobrevin. J Biol Chem 268: 11516–11519PubMedGoogle Scholar
  199. 199.
    Schiavo G, Malizio C, Trimble WS, Polverino de Laureto P, Milan G, Sugiyama H, Johnson EA, Montecucco C (1994) Botulinum G neurotoxin cleaves VAMP/synaptobrevin at a single Ala-Ala peptide bond. J Biol Chem 269: 20213–20216.PubMedGoogle Scholar

Copyright information

© Birkhäuser Verlag/Switzerland 2010

Authors and Affiliations

  • James S. Henkel
    • 1
  • Michael R. Baldwin
    • 2
  • Joseph T. Barbieri
    • 1
  1. 1.Department of Microbiology and Molecular GeneticsMedical College of WisconsinMilwaukeeUSA
  2. 2.Department of Molecular Microbiology and ImmunologyUniversity of MissouriColumbiaUSA

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