Clostridium difficile

Gram positive, obligately anaerobic, spore former. Antibiotic use (e.g. β-lactam antibiotics) reduces concentration of normal microbiota. C. difficile overgrows, produces toxins A and B. Toxins cause diarrhoea & lesions on colon surface which coalesce forming extensive tissue damage – known as pseudomembranous colitis. Can be rapidly fatal. Toxins A and B – large exotoxins that modify host cell membrane G proteins. Mode of action is to alter actin cytoskeleton of mammalian cells. Mediated by toxins glucosylating G-proteins. Glucosyl group (from UDP-glucose) added to specific threonine residue on the G protein.