ctxA

CtxA is the gene encoding the A subunit of cholera toxin in Vibrio cholerae. It resides within the ctxAB operon carried by the CTXφ lysogenic bacteriophage, which can integrate into the bacterial chromosome. The A subunit is produced as part of a single polypeptide that is processed into A1 and A2 fragments, which remain linked by a disulfide bond. Together with five B subunits (CtxB), this forms the AB5 cholera toxin.

The cholera toxin A subunit is an ADP-ribosyltransferase that transfers ADP-ribose from NAD+ to the alpha subunit of the stimulatory G protein (Gs). This modification locks Gsα in an active state, causing sustained activation of adenylate cyclase, elevated intracellular cAMP, and stimulation of the CFTR chloride channel. The resulting efflux of chloride ions and water into the intestinal lumen leads to the profuse watery diarrhea characteristic of cholera.

Expression of ctxA and ctxB is tightly regulated by the ToxR/ToxS virulence regulon and is coordinated with the expression of tcpA, the toxin-coregulated pilus. The CTXφ phage enables phage-encoded ctxA/ctxB genes to propagate, and their expression is influenced by regulatory inputs such as AphA/AphB at low cell density and HapR at high cell density, which modulate virulence gene expression.

CtxA is central to the pathogenic mechanism of cholera. Its study has informed vaccine development, diagnostics, and public health strategies aimed at controlling cholera outbreaks, which are driven by toxin-mediated fluid loss and dehydration.