| Popis: |
Pathogenic strains of Clostridium difficile cause diarrhea and colitis in humans through the release of two protein exotoxins, toxin A and toxin B. This chapter reviews the mechanisms whereby these toxins exert their cytotoxic, enterotoxic, and proinflammatory effects. Antibiotic therapy is the main risk factor for C. difficile infection. C. difficile infection is caused by ingestion of spores. C. difficile infection results in a broad spectrum of clinical manifestations ranging from asymptomatic carriage to severe, life threatening pseudomembranous colitis. Intestinal injury and inflammation result from the effects of C. difficile toxins. C. difficile-associated diarrhea and colitis are usually treated with oral metronidazole or vancomycin to eradicate vegetative forms of the bacterium. C. difficile toxin A and toxin B are the major known virulence factors of C. difficile. These AB-type toxins share similar domains including an N-terminal enzymatic domain responsible for the toxicity of the molecule and a C-terminal binding domain composed of repeating sequences. The observation that neonates and infants are frequently colonized by toxigenic C. difficile but remain asymptomatic suggests that the expression or glucosylation of human intestinal receptors for C. difficile toxins is not complete before the age of 2 years. The translocation of toxin A and toxin B into the cytosol is a prerequisite for their cytotoxic activity. Some bacterial toxins, including diphtheria toxin, translocate from the endosomal compartment to the cytosol following receptor-mediated endocytosis. |
