Pathogenesis of Clostridium difficile-associated diarrhoea

European Journal of Gastroenterology and Hepatology

Volumn 8, Issue 11, 1996, Pages 1041-1047

  Pothoulakis, Charalabos ^a  

^a BETH ISRAEL DEACONESS MEDICAL CENTER   (United States)

Author keywords

Clostridium difficile; Toxin A; Toxin B

Indexed keywords

AMPICILLIN; ANTIBIOTIC AGENT; CELL RECEPTOR; CEPHALOSPORIN; CLOSTRIDIUM DIFFICILE TOXIN A; CLOSTRIDIUM DIFFICILE TOXIN B; GUANINE NUCLEOTIDE BINDING PROTEIN; METRONIDAZOLE; RHO FACTOR; VANCOMYCIN;

ANTIBIOTIC THERAPY; BACTERIAL GENE; BACTERIAL INFECTION; CLOSTRIDIUM DIFFICILE; DIARRHEA; ENTERITIS; HOSPITAL INFECTION; HUMAN; INTESTINE EPITHELIUM CELL; INTESTINE INFECTION; LAMINA PROPRIA; MOLECULAR CLONING; NONHUMAN; NUCLEOTIDE SEQUENCE; PATHOGENESIS; PRIORITY JOURNAL; PSEUDOMEMBRANOUS COLITIS; REVIEW;

EID: 0029802502     PISSN: 0954691X     EISSN: None     Source Type: Journal    
DOI: 10.1097/00042737-199611000-00003     Document Type: Review

References (65)

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54. 17 of the Rho family of proteins by toxin A appears to be the mechanism by which this toxin modifies Rho.
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61. Castagliuolo I, LaMont JT, Letourneau R, Kelly CP, O'Keane JC, • Jaffer A, et al.: Neuronal involvement in the intestinal effects of Clostridium difficile toxin A and Vibrio cholera enterotoxin. Gastroenterology 1994, 107:657-665. Treatment of rats with lidocaine, a local anaesthetic, or hexamethonium, a ganglionic blocker reduced the intestinal effects of toxin A. Pre-treatment with capsaicin, a drug known to desensitize primary sensory neurons which mediate neurogenic inflammation, also dramatically reduced toxin A secretion and inflammation and inhibited toxin A-induced mast cell degranulation in rats. These results indicate that an interaction between sensory neurons and mast cells mediates some of the enterotoxic effects of toxin A.
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63. Pothoulakis C, Castagliuolo I, LaMont JT, Jaffer A, O'Keane JC, •• Snider M, et al.: CP-96,345, a substance P antagonist, inhibits rat intestinal responses to toxin A but not cholera toxin. Proc Natl Acad Sci USA 1994, 91:947-951. The peptide substance P is the major neurotransmitter of capsaic insensitive sensory neurons. Pre-treatment of rats with a highly specific substance P antagonist prevented the enterotoxic effects of toxin A, but not of cholera toxin. This is the first report to indicate that the neuropeptide substance P is involved in enterotoxin-mediated diarrhoea and inflammation.
64. Kelly CP, Becker SD, Linevsky JK, Joshi MA, O'Keane JK, Dickey •• BF, et al.: Neutrophil recruitment in Clostridium difficile toxin A enteritis. J Clin Invest 1994, 93:1257-1265. This study demonstrated the presence of specific toxin A receptors on rabbit neutrophils and presented data to indicate that this receptor is directly coupled to pertussis-sensitive G-proteins. Toxin A directly stimulated neutrophil migration and this effect was also pertussis toxin-sensitive. Furthermore, pre-treatment of rabbits with a blocking monoclonal antibody to the neutrophil adhesion molecule CD18 inhibited toxin A-induced intestinal secretion and inflammation, underscoring the importance of neutrophil recruitment in toxin A enteritis.
65. Kurose I, Pothoulakis C, LaMont JT, Anderson DC, Paulson JC, • Miyasaka M, et al.: Clostridium difficile-induced microvascular dysfunction: Role of histamine. J Clin Invest 1994, 94:1919-1926. Application of toxin A to rat mesenteric venules increased emigration of leucocytes and vascular permeability to albumin. These effects could be inhibited by pre-treatment with monoclonal antibodies directed against the leucocyte adhesion proteins CD11/CD18, or the endothelial adhesion molecules ICAM-1 and P-selectin. Pre-treatment with sialyl Lewis x, a counter receptor for endothelial P-selectin, also inhibited toxin-mediated effects as did HI receptor antagonists, indicating a role for histamine in neutrophil recruitment caused by toxin A.