Clostridium difficile Infection

Abstract

Clostridium difficile infection is associated with broad-spectrum antibiotic therapy and is the most common cause of infectious diarrhea in hospital patients. Pathogenic strains of C. difficile produce two protein exotoxins, toxin A and toxin B, which cause colonic mucosal injury and inflammation. Infection may be asymptomatic, cause mild diarrhea, or result in severe pseudomembranous colitis. Diagnosis depends on the demonstration of C. difficile toxins in the stool. The first step in management is to discontinue the antibiotic that caused diarrhea. If diarrhea and colitis are severe or persistent, oral metronidazole is the treatment of choice. Oral vancomycin is also effective, but it is more expensive than metronidazole and its widespread use may encourage the proliferation of vancomycin-resistant nosocomial bacteria. Diarrhea and colitis usually improve within three days after a patient starts taking metronidazole or vancomycin, but 20% suffer a relapse of diarrhea when these agents are discontinued.

Cholesterol-dependent Pore Formation of Clostridium difficile Toxin A

“…Assays were performed when TER values reached ϳ2000 -3000 ohms⅐cm 2 . TER was determined using a resistance system for electrophysiological readings of filter cups (Endohm-12; World Precision Instruments, Sarasota, FL).…”

Alternative Splicing in Class V Myosins Determines Association with Rab10

“…A sensitive method for monitoring cell intoxication by clostridial toxins is the measurement of the TER of confluent cell monolayers grown on semipermeable filters. For that, enterocytic CaCo-2 cells were grown on filters until starting resistance reached around 2000 -3000 ohms⅐cm 2 . Incubation with methyl-␤-cyclodextrin at concentrations of 0.5, 1, and 2 mM (37°C, 30 min) preceded toxin application (toxin A, 100 ng/ml; ϳ300 pM).…”

“…Regardless of the role of cholesterol, we excluded glycosylphosphatidylinositol (GPI) 2 -anchored structures as possible receptors for both toxins. Consistent with the rubidium release assays, toxin A was able to induce pores in artificial membranes only in the presence of cholesterol.…”

Regulation of toxin synthesis in Clostridium difficile by an alternative RNA polymerase sigma factor

“…1). Virulent strains of C. difficile generally produce two very large protein toxins (ToxA and ToxB) that have been identified as major virulence factors (2).…”