Clostridium difficile (bacteria)

Clostridioides difficile (syn. Clostridium difficile), also known as Peptoclostridium difficile, C. difficile, C. diff (/siː dɪf/), or sometimes Cdi or CDF/cdf, is a species of Gram-positive spore-forming bacterium. Clostridioides are anaerobic, motile bacteria, ubiquitous in nature, and especially prevalent in soil. Its vegetative cells are rod shaped, pleomorphic, and occur in pairs or short chains. Under the microscope, they appear as long, irregular (often drumstick- or spindle-shaped) cells with a bulge at their terminal ends (forms subterminal spores). Under Gram staining, C. difficile cells are Gram-positive and show optimum growth on blood agar at human body temperatures in the absence of oxygen. C. difficile is catalase and superoxide dismutase negative, and produces two types of toxins: enterotoxin A and cytotoxin B, which disrupts cytoskeleton signal transductions in the host. Under stress conditions, the bacteria produce spores that are able to tolerate extreme conditions that the active bacteria cannot tolerate. C. difficile may become established in the human colon; it is present in 2–5% of the adult population. Sometimes antibiotic therapy for various infections has the adverse effect of disrupting the normal balance of the gut microbiota, in which case C. difficile may opportunistically dominate, causing C. difficile infection. The species was transferred from the genus Clostridium to Clostridioides in 2016, thus giving it the new combination Clostridioides difficile. This new name reflects the taxonomic differences between this species and other members of the genus Clostridium, while maintaining the common name as C. diff. As of 2018, the only other species in this new genus Clostridioides is Clostridioides mangenotii (formerly known as Clostridium mangenotii). It had previously been proposed, in a July 2013 paper from Environmental Microbiology, to rename the species Peptoclostridium difficile. Pathogenic C. difficile strains produce multiple toxins. The best-characterized are enterotoxin (C. difficile toxin A) and cytotoxin (C. difficile toxin B), both of which may produce diarrhea and inflammation in infected patients (C. difficile colitis), although their relative contributions have been debated. The diarrhea may range from a few days of intestinal fluid loss to life-threatening pseudomembranous colitis. Pseudomembranous colitis is associated with intense inflammation of the colon and formation of pseudomembranes on the intestinal mucosal surface. Toxins A and B are glucosyltransferases that target and inactivate the Rho family of GTPases. Toxin B (cytotoxin) induces actin depolymerization by a mechanism correlated with a decrease in the ADP-ribosylation of the low molecular mass GTP-binding Rho proteins. There is also a binary toxin (AB toxin), but its role in disease is not fully understood. Additional virulence factors include an adhesin factor which mediate the binding to human colonic cells and a hyaluronidase. The bacterium also produces the chemical para-cresol, which inhibits the growth of other microbes in its vicinity and allows it to outcompete normal human gut flora. Antibiotic treatment of C. diff infections may be difficult, due both to antibiotic resistance and physiological factors of the bacterium (spore formation, protective effects of the pseudomembrane). The emergence of a new, highly toxic strain of C. difficile, resistant to fluoroquinolone antibiotics, such as ciprofloxacin and levofloxacin, said to be causing geographically dispersed outbreaks in North America, was reported in 2005. The U.S. Centers for Disease Control (CDC) in Atlanta warned of the emergence of an epidemic strain with increased virulence, antibiotic resistance, or both. Resistance to other antibiotics such as metronidazole, the first choice of antimicrobial drug when treating CDI, has been observed in up to 12% of clinical isolates, so as treatment with various antibiotics continues, more diverse and stronger resistances will continue to evolve in Clostridium difficile populations, further complicating attempts at effective treatment. Clostridioides difficile is transmitted from person to person by the fecal-oral route. C. difficile is shed in faeces. Any surface, device, or material (e.g., toilets, bathing tubs, and electronic rectal thermometers) that becomes contaminated with faeces may serve as a reservoir for the C. difficile spores. C. difficile spores are transferred to patients mainly via the hands of healthcare personnel who have touched a contaminated surface or item. C. difficile can live for long periods of time on surfaces. The organism forms heat-resistant spores that are not killed by alcohol-based hand cleansers or routine surface cleaning, thus, these spores survive in clinical environments for long periods. Because of this, the bacterium may be cultured from almost any surface. Once spores are ingested, their acid-resistance allows them to pass through the stomach unscathed. They germinate and multiply into vegetative cells in the colon upon exposure to bile acids. Consequently, the World Health Organization advocates the use of soap in addition to alcohol solutions in order to limit the spread of the spores.