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Genetics of Clostridium difficile Toxins

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Book cover Clostridium difficile

Part of the book series: Current Topics in Microbiology and Immunology ((CT MICROBIOLOGY,volume 250))

Abstract

Up until the time it was implicated as the cause of pseudomembranous colitis (PMC), C. difficile was an almost unknown species of bacteria. The organism was first isolated from healthy newborn infants in 1935 by Hall and O’Toole, who named it Bacillus difficilis after the apparent difficulty they encountered in its isolation (Hall and O’Toole 1935). The organism produced a toxic culture filtrate which was lethal to animals upon injection. Perhaps due to the fact that the organism did not appear to cause disease, few studies followed its initial discovery. Over 40 years later, in 1977, C. difficile was implicated as the cause of a lethal colitis that resulted from treatment with antibiotics. The discovery resulted from the finding that antisera to C. sordellii neutralized toxic activity found in fecal filtrates from patients with antibiotic-associated colitis. Curiously, however, C. sordellü could not be isolated from the patients. C. difficile, on the other hand, had been isolated previously from many patients, but had been ignored since it was “nonpathogenic”. Further investigation showed that toxic activity in culture filtrates from C. difficile was neutralized by C. sordellii antisera. Thus the fortuitous cross-neutralizing activity of C. sordellii antisera led to the discovery of C.difficile as the cause of antibiotic-associated colitis.

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References

  • Aktories K (1997) Rho proteins: targets for bacterial toxins. Trends Microbiol 5: 282–288

    Article  PubMed  CAS  Google Scholar 

  • Al-Barrak A, Embil J, Dyck B, Dickson K, Alfa M, Kabani A (1999) An outbreak of toxin A negative, toxin B positive Clostridium difficile-associated diarrhea in a Canadian tertiary-care hospital. Canada Communicable Dis Report 25: 65–69

    CAS  Google Scholar 

  • Alfa M, Lyerly D, Neville L, Moncrief S, Al-Barak A, Kabani A, Dyck B, Dickson K, Embil J (1999) Outbreak of toxin A(—), toxin B(+) Clostridium difficile difficile-associated diarrhea in a Canadian tertiary care hospital. Am Soc Microhiol Ann Meet Abstr, 99th.

    Google Scholar 

  • Arnon SS, Mills DC, Day PA, Henrickson RV, Sullivan NM, Wilkins TD (1984) Rapid death of infant rhesus monkeys injected with Clostridium difficile toxins A and B: physiologic and pathologic basis. J Pediatr 104: 34 40

    Google Scholar 

  • Ball DW, Van Tassel RL, Roberts MD, Hahn PE, Lyerly DM, Wilkins TD (1993) Purification and characterization of alpha-toxin produced by Clostridium novyi type A. Infect Immun 61: 2912–2918

    PubMed  CAS  Google Scholar 

  • Barroso LA, Wang SZ, Phelps CJ, Johnson JI., Wilkins TI) (1990) Nucleotide sequence of the Clostridium difficile toxin B gene. Nucleic Acids Res 18: 4004

    Article  PubMed  CAS  Google Scholar 

  • Barroso LA, Moncriel.IS. Lverly DM, Wilkins TD (1994) Mutagenesis of the Clostridium difficile toxin R gene and effect on cytotoxic activity. Microbial Pathog I6: 297–303

    Article  Google Scholar 

  • Bette P, Frcvert J, Mauler F, Suttorp N, Hahcrmann E (1989) Pharmacological and biochemical studies of the cytotoxicity of Clostridium nom type A alpha toxin. Infect Immun 57: 2507 2513

    Google Scholar 

  • Bette P, Oksche A, Mauler F. Iichel-Streiber Cv, Popoff M R, Hubermaui I: (1991) A comparative biochemical, pharmacological, and immunological study. of ChM Iridiunc nni.ri alpha - toxin. C. ut/uile toxin B and C. sordellii lethal toxin. Toxicon 29: 877–887

    CAS  Google Scholar 

  • Borriello SP, Wren BW, Hyde S, Seddon SV, Sibbons P, Krishna MM, Tabagch,ili S. Manck S, Price AB (1992) Molecular, immunological, and biological characterization of a toxin A-negative toxin B-positive strain of Clostridium difficile. Infect Immun 60: 4192–4199

    CAS  Google Scholar 

  • Borland V, Shao Y. Perna NT, Plunkett G, Sofia HJ, Blattner FR (1998) The complete DNA sequence and analysis of the large virulence plasmid of Clostridium difficile 0157:117. Nucleic Acids Res 20: 4196 4204

    Google Scholar 

  • Busch C, Ilofmann F, Selzer.1, Munro S, Jeckel I), Aktorics K (1998) A common motif of cukaryotic glycosyltrunsferases is essential for the enzyme activity of large clostridia’ toxins. J Biol Chem 273: 19566 19572

    Google Scholar 

  • Castagliuolo I, LaMont JT, Letourneau R, Kelly (’, O’Keane JC. Jailer A.’Lheoharides “LC. Polhoulakis C (1994) Neuronal involvement in the intestinal effects of Clostridium difficile toxin A and t ihrio cholera,enterotoxin in rat ileum. Gastroenterology 11)7:057–665

    Google Scholar 

  • Castagliuolo 1. Keates AC, Oie B. Kelly CP, Nikulasson S. Leeman SE, Polhoulakis C (1997) Increased substance P responses in dorsal root ganglia and intestinal macrophages during Clostridium difficile toxin A enteritis in rats. Proc Natl Acad Sci USA 94: 4788 4793

    Google Scholar 

  • Castagliulo I, Riegler M. Pasha A, Nikulasson, Lu B, Gerard C, Gerard NP, Polhoulakis (’ (1995) Neurokinin-1 (NK-I) receptor is required in Clostridium di/fiei/c-induced enteritis..I Clin Invest 101: 1547 1550

    Google Scholar 

  • Chaves-Olarte L:, Weidmann M. Eichel-Streibcr C. Thclestum M (1997) Toxins A and I3 from Clostridium difficile differ with respect to enzymatic potencies, cellular substrate specificities. and sur0nee binding to cultured cells..1 Clin Invest 1(10:1734–1741

    Google Scholar 

  • Ciesla WP, Bohak DA (1998) Clostridium difficile toxins A and B are cation-dependent Ill)P-Glucose hydrolases with differing catalytic act isities..I Biol Chem 273:16021–1602

    Google Scholar 

  • Cohen SH, Tang YJ, Hansen B, Silva J Jr (1998) Isolation of a toxin B-delienent mutant strain of Clostridium difficile in a case of recurrent C. difficile-associated diarrhea. (’tin Infect Dis 26: 410 412

    Google Scholar 

  • Depitre C, Delmer M, Avesani V, L’Haridon R, Roe’s A, Popoff M. Corthier G (1993) Serogroup E strains of Clostridium difficile produce toxin B but not toxin A..1 Med Microbiol 38: 434 441

    Google Scholar 

  • Dillon ST, Rubin L:J, Yakubovich M. Potholakis C. LaMont.IT, Feig LA, Gilbert RJ (1995) Invobement of Ras-Related Rho proteins in the mechanism of action of Clostridium difficile toxin A and toxin B. Infect Immun 63: 1421 1426

    Google Scholar 

  • Dove CH, Wang S-Z, Price SB, Phelps C.I, Lycrly DM, Wilkins TI). Johnson H. (199(1) Molecular characterization of the Clostridium difficile toxin A gene. Infect Immun 58: 480 488

    Google Scholar 

  • Dupray B, Sonenshein AI. (1998) Regulated transcription of Clostridium difficile toxin genes. Molecular Microbiology 27:107–12(1

    Google Scholar 

  • Ehrich M (1982) I3iochemical and pathological effects of Clostridium difficile toxins in mice Toxicon 20: 983–989

    CAS  Google Scholar 

  • Eichel-Streibcr CV, Suckau D. Wachter M, Hadding U (1988) Cloning and characterization of over- lapping DNA fragments of the toxin A gene of Clostridium difficile.I Gen Microbiol 135: 55 64

    Google Scholar 

  • Eichel-Streiber CV, Sauerborn M (1990) Clostridium difficile toxin A carries a C-terminal repetitive structure homologous to the carbohydrate binding region of streptococcal giscosyl-tnnsferases. (,ene 96: I (17–1 13

    Google Scholar 

  • Eichel-Streiber (’V, Laufenberg-Feldmann R, Sartingen S, Schilze J, Sauerborn M (1992a) Comparative sequence analysis of the Clostridium difficile toxins A and B. Mol Gen Genet 233: 260 268

    Google Scholar 

  • Eichel-Streiber CV, Sauerborn M, Kuramitsu HK (1992b) Evidence for,.c modular structure of the homologous repetitive C-terminal carbohydrate-binding sites of Clostridium difficile toxins and Streptococcus unarms glycosyltranslerases..I Bacteriol 174:671)7–6710

    Google Scholar 

  • Fichel-Streiber CV (1995) Molecular biology of the Clostridium difficile. In: Sebald M (ed) Genetics and molecular biology of the anaerobic bacteria. Springer-Verlag. New York pp 264 289

    Google Scholar 

  • Eichel-Streiber CV, Roquet P. Sauerborn M (1996) Large clostridia’ cytotoxins • Innnily of glucosyl-transferases modifying small GTP-binding proteins. Trends Microbiol 2: 375 382

    Google Scholar 

  • Eklund MW, Poysky FT, Meyers JA, Pelroy GA (1974) Interspecies conversion of Clostridium hontlirmum type C to Clostridium noryi type A by bacteriophage. Science 186: 456–458

    Article  PubMed  CAS  Google Scholar 

  • Eklund MW, Poysky FT, Peterson ME, Meyers JA (1976) Relationship of bacteriophages to alpha toxin production in Clostridium nom types A and B. Infect Immun 14: 793–803

    PubMed  CAS  Google Scholar 

  • Fiorentini C, Malorni W, Paradisi S, Giuliano M, Mastrantonio P, Donelli G (1990) Interaction of Clostridium difficile toxin A with cultured cells: cytoskeletal changes and nuclear polarization. infect Immun 58: 2329–2336

    CAS  Google Scholar 

  • Florin I, Theleslam M (1983) internalization of Clostridium difficile cytotoxin into cultured human lung fibroblasts. Biochim Biophys Acta 763: 383–392

    Google Scholar 

  • Frey S, Wilkins TD (1992) Localization of two epitopes recognized by monoclonal antibody PC’G-4 on Clostridium difficile toxin A. Infect immun 60: 2488–2492

    PubMed  CAS  Google Scholar 

  • Genth II, Hofmann F. Selzer J, Rex G, Aktories K, Just I (1996) Difference in protein substrate specificity between hemorrhagic toxin and lethal toxin from Clostridium sordellii. Biochem Biophys Res Common 229: 370–374

    CAS  Google Scholar 

  • Green GA, Sehne V, Montcil (1995) Cloning and characterization of the cytotoxin L-encoding gene of Clostridium sordellii: homology with Clostridium difficile toxin B. Gene 161: 57–61

    CAS  Google Scholar 

  • Groisman EA, Ochman H (1996) Pathogenicity islands: bacterial evolution in quantum leaps. Cell 87: 791–794

    Article  PubMed  CAS  Google Scholar 

  • Hacker J. Blum-Oehler G, Muhldorfer, Tschape (1997) Pathogenicity islands of virulent bacteria: structure, function and impact on microbial evolution. Mol Microbiol 23: 1089–1097

    Google Scholar 

  • Hagen 1K, Hazes B, Raflo R, de Sa D, Tabak LA (1999) Structure and function of the UDP-Nacetyl-Dgalactosamine: polypeptide N-acetylgalactosaminyltransferase. Essential residues lie in a predicted active site cleft resembling a lactose repressor fold. J Biol Cheni 274: 6797–6803

    Google Scholar 

  • Hall.1, O’Toole E (1935) Intestinal flora in newborn infants with description of a new pathogenic organism, Bacillus difficili.s. Am J Dis Child 135: 390–402

    Google Scholar 

  • Hall A (1998) Rho GTPases and the actin cytoskeleton. Science 279: 509–514

    Article  PubMed  CAS  Google Scholar 

  • Hammond GA, Johnson JL (1995) The toxigenic element of Clostridium difficile strain 10463. Microb Pathog 19: 203–213

    Article  PubMed  CAS  Google Scholar 

  • Hammond GA, Lyerly DM, Johnson JL (1996) Transcriptional analysis of the toxigenic element or Clostridium difficile. Microb Pathog 22: 143–154

    Article  Google Scholar 

  • Hecht G, Pothoulakis C, LaMont JT, Madara JL (1988) Clostridium difficile toxin A perturbs cytoskeletal structure and junction permeability in cultured human epithelial cells. J Clin Invest 82: 1516–1524

    Google Scholar 

  • Henriques B, Florin I, Thelestam M (1987) Cellular internalization of C7o.stridium difficile toxin A. Microb Pathog 2: 455–463

    Article  PubMed  CAS  Google Scholar 

  • Hippensteil S, Tanners-Otto S, Vollrath N, Krull M, Just I, Aktories K, von Eichel-Streiber C, Suttrop N (1997) Glucosylation of the small GTP-binding Rho proteins disrupts endothelial barrier function. Am J Physiol 272:L38 L43

    Google Scholar 

  • Hofmann F, Haberman’) F. von Eichel-Streiber C (1995) Sequencing and analysis of the gene encoding the alpha-toxin of Clostridium noryi proves its homology to toxins A and B of Clostridium difficile. Mol Gen Genet 247: 670–679

    Article  PubMed  CAS  Google Scholar 

  • Hofmann F, Rex G, Aktories K, Just I (1996) The ras-related protein Ral is monoglucosylated by Clostridium.sordrllii lethal toxin. Biochem Biophys Res Commun 227: 77–81

    Article  PubMed  CAS  Google Scholar 

  • Hofmann F, Busch C, Prepens U, Just 1, Aktories K (1997) Localization of the glucosyltransferase activity of Clostridium difficile toxin B to the N-terminal part of the holotoxin..1 Blot Chem 272: 1 1074 11078

    Google Scholar 

  • Hofmann F, Busch C, Aktories K (1998) Chimeric clostridia) cytotoxins: identification of the N-terminal region involved in protein substrate recognition. Infect immun 66: 1076–1081

    PubMed  CAS  Google Scholar 

  • Hundsberger T, Braun V, Weidmann M, Leukel P, Sauerborn M, Eichel-Streiber CV (1997) Transcription analysis of the genes tcd,4-E of the pathogenicity locus of Clostridium difficile. Fur J Biochem 244: 735–742

    CAS  Google Scholar 

  • Johnson JL, Phelps (’J, Barroso LA, Roberts MD, Lyerly DM, Wilkins TD (1990) Cloning and expression of the toxin B gene of Clostridium difficile. Curr Microbiol 20: 397–401

    CAS  Google Scholar 

  • Just I, Fritz G, Aktories K, Giry M, Popoff MR, Boquet P, Hegenbarth S, Eichel-Streiber CV (1994) Clostridium difficile toxin B acts on the GTP-binding protein Rho. J Biol Chem 269: 10706–10712

    Google Scholar 

  • Just I, Selzer J, Eichel-Streiber Cv, Aktories K (1995a) The low molecular mass GTP-binding protein Rho is affected by toxin A from Clostridium difficile. J Clin Invest 95: 1026–1031

    Article  PubMed  CAS  Google Scholar 

  • Just I, Selzer J, Wilm M, Eichel Streiber Cv, Mann M, Aktories K (1995h) Glucosylation of Rho proteins by Clostridium difficile toxin B. Nature 375: 500–503

    Article  PubMed  CAS  Google Scholar 

  • Just I, Wilm M, Selzer J, Rex G, Eichel Streiber Cv, Mann M, Aktories K (1995c) “[he enterotoxin from Clostridium diJ/mile (ToxA) monoglucosylates the Rho proteins..I Biol (’hem 270: 13932 13939

    Google Scholar 

  • Just I, Selzer J, Hofmann F, Green GA, Aktories K (1996) Inactivation of Ras by Clostridium sorrlellii lethal toxin-catalyzed glucosylation. J Biol Chem 271: 10149 I0153

    Google Scholar 

  • Kato H, Kato N, Wantabc K, Iwai N, Nakamura IL Yamamoto T, Suzuki K, Kim S-M. Chong Y. Wasito EB (1998) Identification of toxin A-negative, toxin B-positive Clostridium eli_f/icile by PCR.,1 Clin Microbiol 36: 2178–2182

    CAS  Google Scholar 

  • Krivan HC, Clark GF, Smith DF,Wilkins TI) (1986) Cell surface binding site for Clostridium di//irilr enterotoxin: evidence for a glycoconjugate containing the sequence Gal5(1–3Galßl-4(ì1eNAc. Infect immun 53: 573 581

    Google Scholar 

  • Libby JM, Jortner BS, Wilkins TD (1982) Effects of the two toxins of clostridium dì%flri/e in antibiotic-associated cecitis in hamsters. Infect Immun 36: 822–829

    PubMed  CAS  Google Scholar 

  • Lima AAM, Lyerly I)M, Wilkins TD, lines DJ, Guerrant RL (1988) Effects of Clostridium difficile toxins A and B in rabbit small and large intestine in vivo and on cultured cells in vitro. missi Immun 56: 582–588

    CAS  Google Scholar 

  • Lyerly DM, Lockwood DE, Richardson SH, Wilkins TI) (1982) Biological activities of toxins A and B of Clostridium difficile. Infect Immun 35:1 147–1 150

    Google Scholar 

  • Lyerly DM, Sullivan NM, Wilkins TD (1983) Enzyme-linked immunosorbcnl assay Ior Clostridium difficile toxin A..1 Clin Microbiol 17: 72–78

    CAS  Google Scholar 

  • Lyerly DM, Saum KE, MacDonald DK, Wilkins TI) (1985) Effects of Clostridium dif/ici/e toxins given intragastrically to animals. Infect Immun 47: 349 352

    Google Scholar 

  • Lyerly DM, Roberts MD, Phelps (’J, Wilkins TI) (1986) Purification and properties of toxins A and B of Clostridium d/me FEMS Microbiol Lett 33: 31 35

    Google Scholar 

  • Lyerly DM, Barroso LA, Wilkins TI), Depitre C, Corthier G (1992) Characterization of u toxin A-negative, toxin B-positive strain of Clostridium difficile. Infect Immun 60: 4633 4639

    Google Scholar 

  • Lyerly DM. Wilkins TD (1995) Clostridium dif/lei/e. In: Blaser M.I, Smith PD. Ravdin JI, Greenberg I IB, (inerrant RL (eds) Infections of the Gastrointestinal Tract. Raven Press, New York, pp 867–891

    Google Scholar 

  • Makay DJG, Hall A (1998) Rho GTPases. J Biol Chem 273: 20685–20688

    Article  Google Scholar 

  • Manyth CR, Maggio JE, Mantyth PW, Vigna SR, Pappas TN (1996a) Increased substance l’ receptor expression by blood vessels and lymphoid tissue aggregates in Clostridium r/i//ici/e-induced pseudo-membranous colitis. Dig Dis Sei 41: 614–620

    Article  Google Scholar 

  • Mantyh CR, Pappas TN, Lapp JA, Washington MK, Neville LM, Ghilardi JR, Rogers SD. Manyth PW. Vigna SR (1996b) Substance P activation of enteric neurons in response to intraluminal Clostridium difficile toxin A in the rat ileum. Gastroenterology 111: 1272 1280

    Google Scholar 

  • Martinez RD, Wilkins TD (1988) Purification and characterization of Clostridium surr/el/ii hemorrhagic toxin and cross-reactivity with Clostridium difficile toxin A (enterotoxin). Infect Immun 56: 1215 1221

    Google Scholar 

  • Martinez RD, Wilkins TD (1992) Comparison of Clostridium.sortie!/ü toxins If I“ and I.T with toxins A and B of C. dif/icile..1 Med Microbiol 36: 30–36

    CAS  Google Scholar 

  • Marvaud JC, Eisen Il, Binz T, Nieman II, Popoff MR (1998) TetR is a positive regulator of the tetanus toxin gene in Clostridium tetaai and is homologous to bot R. Infect Immun 66: 5698–5702

    PubMed  CAS  Google Scholar 

  • Marvaud JC, (iihert M, Inoue K, Fujinaga Y, Ogunra K, Popoff MR (1998) botR“A is a positive regulator of the hotulinum neurotoxin and associated non-toxin protein genes in Clostridium hotu/iumn A. Mol Microbiol 29: 1009–1018

    Google Scholar 

  • Missiakas I), Raina S (1998) The extracytoplasmic function factors: role and regulation. Mol Microbiol 28: 1059–1066

    Article  PubMed  CAS  Google Scholar 

  • Mitchell J, Laughon BE, Lin S (1987) Biochemical studies on the clfect of Clostridium difficile toxin B on actin in vivo and in vitro. Infect Immun 55:161(1–1615

    Google Scholar 

  • Moncrief JS, Barroso LA, Wilkins Ti) (1997a) Positive regulation of C7nstriditun di//iei/e toxins. Infect Immun 65: 1105–1108

    PubMed  CAS  Google Scholar 

  • Moncrief JS, Lyerly DM, Wilkins TD (1997h) Molecular biology of the Clostridium difficile toxins. In: Rood JI, Songer G, McClane B, Tithall R (eds) Molecular Genetics and Pathogenesis of the Clostridia. Academic Press, London, pp 369–392

    Google Scholar 

  • Moncrief JS, Duncan AJ, Wright RL, Barroso LA, Wilkins TD (1998) Molecular characterization of the fragilysin pathogenicity islet of enterotoxigenic Bacteroides /ragi/is. Infect Immun 66: 1735 1739

    Google Scholar 

  • Moncrief JS, Neville LM, Lyerly DM (1999) Molecular characterization of toxin A-negativetoxin B-positive strains of Clostridium difficile. Am Soc Microbiol, Ahstr Ann Meet. 99th

    Google Scholar 

  • Muldrow LL. Iheanu GC, Lee NI, Bose NK, Johnson.1 (1987) Molecular cloning of Clostridium (Wile toxin A gene fragment in lambdas gt1 L FEBS Lett 213: 249 253

    Google Scholar 

  • Mullany P, Wilks M, Lamb 1, Clayton C, Wren B, Tobaqchali S (1990) Genetic analysis of a tetracycline resistance element from Clostridium difficile and its conjugal transfer to and from Bacillus subtilis. J Gen Microbiol 136:1343 -I349

    Google Scholar 

  • Mullany P, Wilks M, Tobaqchali S (1991) Transfer of Tn9/6 and Tn9/6AE into Clostridium difficile: demonstration of a hot spot for these elements in the C. difficile genome. FEMS Microbiol Lett 79: 191–194

    CAS  Google Scholar 

  • Mullany P, Wilks M, Puckey L, Tabagchali S (1994) Gene cloning in Clostridium difficile using Tn9/6 as a shuttle conjugative transposon. Plasmid 31: 320–323

    Article  PubMed  CAS  Google Scholar 

  • Ottlinger ME, Lin S (1988) Clostridium difficile toxin B induces reorganization of actin, vinculin and talin in cultured cells. Exp Cell Res 174: 215–229

    Google Scholar 

  • Phelps CJ, Lyerly DM, Johnson JL, Wilkins Ti) (1991) Construction and expression of the complete Clostridium difficile toxin A gene in Escherichia coli. Infect immun 59:I50N53

    Google Scholar 

  • Popoff MR (1986) Purification and characterization of Clostridium sordel/ii lethal toxin and cross-reactivity with Clostridium difficilr cytotoxin. Infect immun 55: 35–43

    Google Scholar 

  • Popoff MR, Chaves-Olarte E, Lemichez E, von Eichel-Streiber C, Thelstam M, Chardin P, Cusssac D, Antony B, Chavier P, Flatau G, Giry M, de Gunzburg J, Boquet P (1996) Ras, Rap, and Rae small GTP-binding proteins are targets for Clostridium sordellii lethal toxin glucosylation. J Biol Chem 271: 10217–10224

    Article  PubMed  CAS  Google Scholar 

  • Pothoulakis C, C’astigiuolo I, LaMont JT, Jaflèr A, O’Keane JC, Snider RM, Leeman SE (1994) CP96,345, a substance P antagonist inhibits rat intestinal responses to Clostridium difficile toxin A but not cholera toxin. Proc Natl Acad Sci USA 91: 947–951

    Article  PubMed  CAS  Google Scholar 

  • Pothoulakis C, Gilbert RJ, Cladaras C, Castagliuolo i, Semenza G, Hitti Y, Moncrief JS, Linevsky J, Kelly CP, Nikulasson S, Desai HP, Wilkins TD, LaMont JT (1996) Rabbit sucrase-isomaltase contains a functional intestinal receptor for Clostridium difficile toxin A. J Clin Invest 98: 641 649

    Google Scholar 

  • Pothoulakis C, Castagliuolo I, Leeman SE, Wang CC, Li H, Hofmann BJ, Mezey E (1998) Substance P receptor expression in intestinal epithelium in Clostridium difficile toxin A enteritis in rats. Am J Physiol 275: G68–675

    PubMed  CAS  Google Scholar 

  • Price SB, Phelps CJ, Wilkins TD, Johnson JL (1987) Cloning of the carbohydrate binding portion of the toxin A gene of Clostridium diffcile. Curer Microbiol 16: 55–60

    Article  CAS  Google Scholar 

  • Riegler M, Sedivy R, Pothoulakis C, Hamilton G, Johannes Z, Bischof G, Costentini E, Wolfgang F, Schiessel, LaMont JT, Wenzl E (1995) Clostridium difficile toxin B is more potent than toxin A in damaging human colonic epithelium in vitro. J Clin Invest 95: 2004–2011

    Google Scholar 

  • Rupkin M, Braun V, Soehn F, Jane M, Hofstetter M, Laufenberg-Feldmann R, von Eichel-Streiber C (1997) Characterization of polymorphisms in the toxin A and B genes of Clostridium difficile. FEMS Microbiol Lett 148: 197 202

    Google Scholar 

  • Rupkin M, Avesani V, Jane M, Eichel-Streiber Cv, Delmee M (1998) A novel toxinotyping scheme and correlation of toxinotypes with serogroups of Clostridium difficile isolates. J Clin Microbiol 36: 2240–2247

    Google Scholar 

  • Sehr P, Joseph G, Genth H, Just i, Pick E, Aktories K (1998) Glucosylation and ADP ribosylation of rho proteins: e0ects on nucleotide binding, GTPase activity, and effector coupling. Biochemistry 37: 5296–5304

    Google Scholar 

  • Selzer J, Hofmann F, Rex G, Wilm M, Mann M, Just 1, Aktories K (1996) Clostridium nervi alpha-toxin-catalyzed incorporation of GIcNAc into Rho subfamily proteins. J Biol Chem 271: 25173–25177

    Google Scholar 

  • Smith JA, Cooke DL, Hyde S, Borrielo SP, Long (1997) Clostridium diflicle binding to human epithelial cells. J Med Microbiol 46: 953–958

    Google Scholar 

  • Soehn F, Wagenknecht-Wiesner A, Leukel P, Kohl M, Weidmann M, von Eichel-Streiber C, Braun V (1998) Genetic rearrangements in the pathogenicity locus of Clostridium difficile strain 8864 - implications for the transcription, expression and enzymatic activity of toxin A and B. Mol Gen Genet 258: 222 2. 32

    Google Scholar 

  • Song KP, Faust C (1998) Molecular analysis of the promoter region of the Clostridium difficile toxin B gene that is functional in Escherichia roll. J Med Microbiol 47: 309–316

    Article  PubMed  CAS  Google Scholar 

  • Sterne M, Wentzel LM (1950) A new method for the large scale production of high titre botulinum Formal-toxoid types C and D. J Immunol 65: 175–183

    PubMed  CAS  Google Scholar 

  • Thelestam M, Bronnegard M (1980) Interaction of cytopathogenic toxin from Clostridium difficile with cells in tissue culture. Scand.I Infect Dis 22: 16 29

    Google Scholar 

  • Torres,1F (1991) Purification and characterization of toxin B from a strain of Clostridium difficile that does not produce toxin A. J Med Microbiol 35: 40–44

    Article  PubMed  CAS  Google Scholar 

  • Tucker KD, Carrig PE, Wilkins TI) (1990) Toxin A of Clostridium diide is a potent cytotoxin. J Clin Microbiol 28: 869 871

    Google Scholar 

  • Tucker K, Wilkins TD (1991) Toxin A of C7osnidium di//ìcle hinds to the human carbohydrate antigens I, X, and Y. Infect Immun 59: 73–78

    Google Scholar 

  • Wagenknecht-Wiesner A, Weidmann M, Braun V, Leukel P, Moos M. on I ichel-Streiher (’v (1997) Delineation of the catalytic domain of the C/osiridirnn di%flci/e toxin B-10463 to an enigmatically active N-terminal 467 amino acid fragment. FEMS Microbiol Felt 152: 109 116

    Google Scholar 

  • Wren BW, Clayton CL, Mullany PP, Tabagchali S (1989) Molecular cloning and expression of (/ostridiunr difficile toxin A in Escherichiu soli K 12. FIBS Lett 225: 82 86

    Google Scholar 

  • Yamakawa K, Karasava T, Ikoma S, Nakamura S (1996) Enhancement of Clostridium difficile toxin production in biotin-limited conditions..1 Med Microbiol 44: 111 114

    Google Scholar 

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© 2000 Springer-Verlag Berlin Heidelberg

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Moncrief, J.S., Wilkins, T.D. (2000). Genetics of Clostridium difficile Toxins. In: Aktories, K., Wilkins, T.D. (eds) Clostridium difficile. Current Topics in Microbiology and Immunology, vol 250. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-662-06272-2_2

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  • DOI: https://doi.org/10.1007/978-3-662-06272-2_2

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