PHASE VARIATION IN TCPH MODULATES EXPRESSION OF THE TOXR REGULON IN VIBRIO-CHOLERAE

We evaluated a spontaneous mutant of Vibrio cholerae, which was avirul ent in an infant mouse and had reduced expression of cholera toxin and TcpA in response to environmental signals. The toxR, toxS and toxT ge nes in the mutant were normal, but transcription of toxT was absent. A plasmid expressing wild-type tcpP and tcpH complemented the mutant. T he mutation resulted from a frameshift in a string of nine G residues within tcpH; similar slipped-strand mutations in tcpH arose at a frequ ency of 10(-4) during overnight growth and in the majority of colonies by the end of 5 days of growth in ToxR-inducing conditions. Transcrip tion of tcpPH was regulated by temperature and pH independently of Tox R or ToxT. These results suggest that TcpH couples environmental signa ls (temperature and pH) to expression of the ToxR regulon, and provide a model for phase variation in the cc-ordinate expression of cholera virulence factors.