Clostridium difficile cytotoxin

It has been postulated that Chlamydia may produce a heat shock protein that causes tissue damage through a delayed hypersensitivity reaction. C. trachomatis may also possess DNA evidence of toxin-like genes that code for high-molecular-weight proteins with structures similar to Clostridium difficile cytotoxins, enabling inhibition of immune activation. This may explain the observation of a chronic C. trachomatis infection in subclinical PID. 

Taylor NS, Bartlett JG. Binding of Clostridium difficile cytotoxin and vancomycin by anion-exchange resins. J Infect Dis 1980 141(l) 92-7. 

Eichel-Streiber Cv, Meyer zu Heringdorf D, Habermann E, et al. (1995) Closing in on the toxic domain through analysis of a variant Clostridium difficile cytotoxin B. In Molec. Microbiol. 17 313-321. 

Florin I, Thelestam M (1983) Internalization of Clostridium difficile cytotoxin into cultured human lung fibroblasts. In Biocbim. Biophys. Acta, 763 383-392. 

Green GA, Schue V, Monteil H (1995) Cloning and characterization of the cytotoxin L-encoding gene of Clostridium sordellii homology with Clostridium difficile cytotoxin B. In Gene, 161 57-61. 

Schu6V, Green GA, Girardot R, etal. (1994) Hyperphosphorylation of calnexin, a chaperone protein, induced by Clostridium difficile cytotoxin. In Biochem. Bio-phys. Res. Commun. 203 22-28. 

Although immediate reactions of anaphylaxis, bronchospasm, and urticaria have been reported, most commonly patients exhibiting an adverse reaction develop a maculopapular rash, usually after several days of therapy. They may also develop fever and eosinophilia (80,219). Cefoperazone (34) and ceftriaxone (39), having greater biUary excretion than other cephalosporins, are associated with an increased risk of diarrhea, which may be caused by selection of cytotoxin producing stains of Clostridium difficile (219). 

Important members of this toxin family are Clostridium difficile toxins A and B, which are implicated in antibiotics-associated diarrhea and pseudomembranous colitis. The large clostridial cytotoxins are single-chain toxins with molecular masses of 250-308 kDa. The enzyme domain is located at the N terminus. The toxins are taken up from an acidic endosomal compartment. They glucosylate RhoA at Thr37 also, Rac and Cdc42 are substrates. Other members of this toxin family such as Clostridium sordellii lethal toxin possess a different substrate specificity and modify Rac but not Rho. In addition, Ras subfamily proteins (e.g., Ras, Ral, and Rap) are modified. As for C3, they are widely used as tools to study Rho functions [2] [4]. 

Clostridium difficile is a commensal Gram-positive anaerobic bacterium of the human intestine, found in about 2-5% of the population. C. difficile is the most serious cause of antibiotic-associated diarrhoea and can lead to pseudomembranous colitis, a severe infection of the colon, often resulting from eradication of the normal gut flora by antibiotics. Discontinuation of causative antibiotic treatment is often curative. In more serious cases, oral administration of metronidazole or vancomycin is the treatment of choice. The bacterium produces several known toxins, including enterotoxin (toxin A) and cytotoxin (toxin B), both of which are responsible for the diarrhoea and inflammation seen in infected patients another toxin, binary toxin, has also been described. 

Clostridium difficile can be cultured from the stool, and toxins A and B can be assessed by different techniques (116). The most accurate method is still a cytotoxin tissue culture assay. This detects the cytopathic effect of cytotoxin B, which can be neutralized by Clostridium sordellii antitoxin, but it takes 24 8 hours to show a result. Alternative tests that produce faster results have been developed. A latex agglutination test lacks sensitivity and specificity, and does not distinguish toxigenic from non-toxigenic strains. An enzyme immunoassay for toxin A may be an acceptable alternative to the cell cytotoxin assay and the results are rapidly available. A dot immunobinding assay has not yet been extensively studied (164). 

Woods GL, Iwwen PC. Comparison of a dot immunobind-ing assay, latex agglutination, and cytotoxin assay for laboratory diagnosis of Clostridium difficile-associated diarrhea. J Clin Microbiol 1990 28(5) 855-7. 

Ahlgren T, Florin I, Jarstrand C, et al. (1983) Loss of surface fibronectin from human lung fibroblasts exposed to cytotoxin from Clostridium difficile. In Infect. Immun. 39 1470-1472. 

Corthier, G., Dubos, F., and Raibaud, P, Modulation of cytotoxin production by Clostridium difficile in the intestinal tracts of gnotobiotic mice inoculated with various human intestinal bacteria, Appl. Environ. Microbiol., 49, 250, 1985. 

Clostridium difficile is a Gram-positive bacteria, spore-forming, responsible for 15-20% of the antibiotic-associated diarrhoeas (Hamrick et al. 1989 Eckel et al. 2002). The gold-standard technique for the detection of Clostridium difficile is the stool cytotoxin assay. The microbiological mechanism is related to the production of two toxins (toxins A and B) by Clostridium difficile (Kyne et al. 2000). Disturbance of the normal bacterial flora in the colonic lumen is an important factor for the development of PMC (Ros et al. 1996). Children younger than 1 year develop symptomatic disease probably because of immature enterocytic membrane receptors for the toxin (Ros et al. 1996). 

---