Clostridioides difficile toxin B

C Diff ToxB 2BVM

Clostridioides difficile toxin B (TcdB) is a potent cytotoxin produced by the bacterium Clostridioides difficile. It is one of the primary virulence factors responsible for the symptoms of Clostridioides difficile infection (CDI), which can range from mild diarrhea to severe pseudomembranous colitis.

Structure and Function

TcdB is a large protein that belongs to the family of Rho-glucosylating toxins. It is composed of several domains, each responsible for different aspects of its function. The toxin is known to inactivate small GTPases of the Rho family, including RhoA, Rac1, and Cdc42, by glucosylation. This inactivation disrupts the actin cytoskeleton, leading to cell rounding and death.

Mechanism of Action

Upon entering the host cell, TcdB undergoes endocytosis and is transported to the endosome. Acidification within the endosome triggers a conformational change in the toxin, allowing it to translocate its enzymatic domain into the cytosol. Once in the cytosol, TcdB glucosylates Rho GTPases, leading to the disruption of the actin cytoskeleton, loss of cell adhesion, and ultimately cell death.

Role in Disease

TcdB, along with Clostridioides difficile toxin A (TcdA), is a major contributor to the pathogenesis of CDI. The toxins cause damage to the intestinal epithelium, leading to inflammation, increased intestinal permeability, and diarrhea. In severe cases, the toxins can cause pseudomembranous colitis, characterized by the formation of pseudomembranes on the colonic mucosa.

Diagnosis and Treatment

The presence of TcdB in stool samples is a key diagnostic marker for CDI. Diagnostic methods include enzyme immunoassays (EIA), polymerase chain reaction (PCR) assays, and cell cytotoxicity neutralization assays. Treatment of CDI typically involves the use of antibiotics such as metronidazole, vancomycin, or fidaxomicin. In recurrent cases, fecal microbiota transplantation (FMT) may be considered.

Prevention

Preventive measures for CDI include proper hand hygiene, use of personal protective equipment, and judicious use of antibiotics to reduce the risk of disrupting the normal gut microbiota.

Related Pages

• Clostridioides difficile
• Clostridioides difficile infection
• Clostridioides difficile toxin A
• Pseudomembranous colitis
• Rho family of GTPases
• Fecal microbiota transplantation