Clostridium difficile colitis: pathogenesis and host defence

Abstract

Clostridium difficile is a major cause of intestinal infection and diarrhoea in individuals following antibiotic treatment. Recent studies have begun to elucidate the mechanisms that induce spore formation and germination and have determined the roles of C. difficile toxins in disease pathogenesis. Exciting progress has also been made in defining the role of the microbiome, specific commensal bacterial species and host immunity in defence against infection with C. difficile. This Review will summarize the recent discoveries and developments in our understanding of C. difficile infection and pathogenesis.

The Design, Synthesis, and Characterizations of Spore Germination Inhibitors Effective against an Epidemic Strain of Clostridium difficile

“…1 These spores are highly resistant to harsh environmental factors such as stomach acid, extreme temperatures, and pharmaceutically relevant antibiotics. 5 As the spores travel through the gastrointestinal tract, various endogenous bile salts stimulate the spores to germinate into vegetative, toxin 1,5–10 .producing C. difficile cells. In most cases, the vegetative C .…”

Interspecies Interactions between Clostridium difficile and Candida albicans

“…Inhibition of Candida hypha formation by C. difficile may also be relevant for recurrent CDI. A positive effect of C. albicans on the regeneration of the intestinal flora after antibiotic-induced dysbiosis was recently shown (29), and reestablishment of a diverse gut microbiome is accompanied by a decreasing probability for the development of CDI (2, 10). By inhibiting hypha formation, C. difficile can prolong the window of opportunity for the development of CDI as it competes directly with C. albicans itself or by competing with bacteria in a heterogeneous C. albicans -containing biofilm.…”

“…Clostridium difficile is a Gram-positive, obligate anaerobic, endospore-forming bacterium that is one of the most important causes of health care-associated infections (1, 2). Patients infected with C. difficile show symptoms that range from mild diarrhea to severe colitis—inflammation of the large intestine—that can lead to death (3).…”

“…The current estimate is that 500,000 cases of CDI are diagnosed each year in the United States and 124,000 in Europe (1). Of these 500,000 cases, an estimated 4% of the patients never recover and eventually die (2, 10). The costs associated with CDI, an estimated $1 to $3 billion annually in the United States alone, represent a significant problem in health care settings (11, 12).…”

“…The combined effect is that C. difficile can thrive while other bacteria in the intestinal flora suffer (15, 16). The risk of CDI declines once antibiotic treatment is completed and the gut microbiome can restore its original diversity and strength (2). …”