TCDB

tcdB is the gene encoding toxin B, one of the major virulence factors produced by the pathogenic bacterium Clostridioides difficile. TcdB is a large protein that functions as a glucosyltransferase toxin, contributing to cytotoxic effects on intestinal epithelial cells and driving the inflammatory response seen in severe C. difficile infections.

Genetically, tcdB is part of the pathogenicity locus (PaLoc) in C. difficile, a distinct cluster that also includes the toxin A gene (tcdA) and regulatory elements that control toxin production. Variation in tcdB alleles across strains can influence the potency and antigenic properties of the toxin, and certain lineages known for hypervirulence produce highly active TcdB variants.

Mechanistically, TcdB binds to host cells and is internalized by endocytosis. Inside the cell, the toxin undergoes proteolytic processing to release its glucosyltransferase domain, which then glucosylates Rho family GTPases. This modification disrupts actin cytoskeleton dynamics, cell junctions, and signaling pathways, leading to cell rounding, loss of barrier function, and cell death.

Clinical and diagnostic relevance centers on toxin detection and disease severity. Toxigenic C. difficile strains are identified by the presence of tcdB (often alongside tcdA) in diagnostic assays. TcdB is considered a key driver of disease severity in many infections, and therapies targeting toxin B, along with standard antimicrobial treatment, are central to management. CDT, the binary toxin encoded by cdtA and cdtB, is a separate virulence factor found in some strains.