Enterotoxic clostridia: Clostridioides difficile infections

Clostridioides difficile is a Gram-positive anaerobic, spore-forming bacterium and the most common identifiable infectious agent of nosocomial antibiotic-associated diarrhea (AAD) (1, 2). This bacterium is also linked to several life-threatening syndromes in humans, including pseudomembranous colitis and toxic megacolon (1, 2). Disease symptoms associated with C. difficile infection (CDI), including diarrhea, fluid loss, and inflammation, result from the production and activity of two exotoxins, toxin A (TcdA) and toxin B (TcdB) (2). These toxins disrupt the Rho family of GTPases within the host cell, which eventually results in cell rounding and death (3, 4). C. difficile was originally discovered by Hall and O’Toole as Bacillus difficilis during their 1935 study of neonatal fecal microbiota and was named “difficilis” due to the difficulty of its cultivation and isolation (5). At the time of its initial isolation, C. difficile was not considered pathogenic, with recognition of C. difficile as a human pathogen occurring roughly 40 years after its initial discovery (5). With time, identification of the obligately anaerobic nature of this organism ultimately resulted in reclassification from B. difficilis to Clostridium difficile. More recently, with an update to the classification of the clostridia, it was first suggested that C. difficile be reclassified as Peptoclostridium difficile (6) and, more recently, to Clostridioides difficile (7). However, as recently highlighted in Smits et al. (8), there is reluctance for reclassification, because there currently exists a large knowledge base surrounding Clostridium difficile, in addition to a strong public awareness which could be lost upon reclassification. Despite these reservations, Clostridioides difficile has now been officially approved by the International Journal of Systematic and Evolutionary Microbiology and International Committee on Systematics of Prokaryotes and has begun to be used more commonly (9-11).