Clostridium difficile: its disease and toxins

Abstract

Clostridium difficile is the etiologic agent of pseudomembranous colitis, a severe, sometimes fatal disease that occurs in adults undergoing antimicrobial therapy. The disease, ironically, has been most effectively treated with antibiotics, although some of the newer methods of treatment such as the replacement of the bowel flora may prove more beneficial for patients who continue to relapse with pseudomembranous colitis. The organism produces two potent exotoxins designated toxin A and toxin B. Toxin A is an enterotoxin believed to be responsible for the diarrhea and mucosal tissue damage which occur during the disease. Toxin B is an extremely potent cytotoxin, but its role in the disease has not been as well studied. There appears to be a cascade of events which result in the expression of the activity of these toxins, and these events, ranging from the recognition of a trisaccharide receptor by toxin A to the synergistic action of the toxins and their possible dissemination in the body, are discussed in this review. The advantages and disadvantages of the various assays, including tissue culture assay, enzyme immunoassay, and latex agglutination, currently used in the clinical diagnosis of the disease also are discussed.

Toxins, Butyric Acid, and Other Short-Chain Fatty Acids Are Coordinately Expressed and Down-Regulated by Cysteine in Clostridium difficile

“…Its key virulence factors are two toxins, A and B, which are members of the large clostridial cytotoxin family and thus have high molecular weight and conserved protein domains and enzymatic function (21). The onset of C. difficile growth in the large intestine, followed by C. difficile-associated diarrhea (CDAD), is thought to be caused by the reduction of protective colonic microbiota, especially by antibiotic treatment (14). Toxin production by C. difficile has been demonstrated to be dependent on the nutrient level of the growth medium (7,10,12,18,24,25).…”

“…Clostridium difficile is the etiologic agent of pseudomembranous colitis and a major cause of antibiotic-associated diarrhea (14). Its key virulence factors are two toxins, A and B, which are members of the large clostridial cytotoxin family and thus have high molecular weight and conserved protein domains and enzymatic function (21).…”

Laboratory Diagnosis of Clostridium difficile Infection

“…It is found in humans, a variety of animals, and the environment. 13,14 Two toxins, designated A and B, encoded by the chromosomal genes tcdA and tcdB, respectively, are part of a pathogenicity locus (PaLoc) that is typically present in those strains of C. difficile that cause disease. The toxins are regulated by two additional genes, tcdC and tcdR; a holinlike protein is also encoded by tcdE.…”

“…In addition, the mean sensitivity of membrane-type GDH assays in the ESCMID survey was only 60% when compared with toxigenic culture, 3 suggesting that GDH screening may not be as highly sensitive as previously assumed. 13 A recent meta-analysis of GDH tests by Shetty and colleagues 45 reported that, when compared with the results of toxigenic culture, the sensitivity of GDH assays ranged from a low of 79.2% to 98% and varied with the prevalence of CDI. This, along with the data on GDH sensitivity reported by Peterson and Robicsek, 5 calls into question the utility of a two-step approach.…”

“…Laboratory Detection of CDI 577 JMD November 2011, Vol. 13,No. 6 istration (FDA)-cleared nucleic acid amplification assays for laboratory diagnosis of CDI, based on their respective package inserts, is shown in Figure 2.…”