Differential transcription of the tcpPH operon confers biotype-specific control of the Vibrio cholerae ToxR virulence regulon

Epidemic strains of Vibrio cholerae O1 are divided into two biotypes, class ical and El Tor. In both biotypes, regulation of virulence gene expression depends on a cascade in which ToxR activates expression of ToxT, and ToxT a ctivates expression of cholera toxin and other virulence genes. In the clas sical biotype, maximal expression of this ToxR regulon in vitro occurs at 3 0 degrees C at pH 6.5 (ToxR-inducing conditions), whereas in the El Tor bio type, production of these virulence genes only occurs under very limited co nditions and not in response to temperature and pH; this difference between biotypes is mediated at the level of toxT transcription. In the classical biotype, two other proteins, TcpP and TcpH, are needed for maximal toxT tra nscription. Transcription of tcpPH in the classical biotype is regulated by pll and temperature independently of ToxR or ToxT, suggesting that TcpP an d TcpH couple environmental signals to transcription of toxT. In this study , we show a near absence of tcpPH message in the El Tor biotype under ToxR- inducing conditions of temperature and pH. However, once expressed, El Tor TcpP and TcpH appear to be as effective as classical TcpP and TcpH in activ ating toxT transcription. These results suggest that differences in regulat ion of virulence gene expression between the biotypes of V. cholerae primar ily result from differences in expression of tcpPH message in response to e nvironmental signals. We present an updated model for control of the ToxR v irulence regulon in V. cholerae.