The ability of the intestinal pathogen Vibrio cholerae to undergo an adaptive stress response, known as the acid tolerance response (ATR), was previously shown to enhance virulence. An essential component of the ATR is CadA-mediated lysine decarboxylation. CadA is encoded by the acid- and infection-induced gene cadA. Herein, cadA is shown to be the second gene in an operon with cadB, encoding a lysine/cadaverine antiporter. cadC, which is 5' of cadB, encodes an acid-responsive, positive transcriptional regulator of cadBA. Unlike in Escherichia coli, V. cholerae cadB and cadA are also transcribed monocistronically. Of note, bicistronic cadBA is transcribed at low constitutive levels in an acid- and CadC-independent manner. CadC represents a new member of the "ToxR-like" family of transcriptional regulators in V. cholerae and, in addition, exhibits extensive amino acid and functional similarity to E. coli CadC. The amino-terminal, putative DNA binding domains of ToxR and CadC are highly conserved, as are the putative promoter elements recognized by these transcription factors.