ToxR regulates virulence gene expression in non-O1 strains of Vibrio cholerae that cause epidemic cholera

Vibrio cholerae serogroup O1 has historically been thought to be the exclusive cause of epidemic cholera. O139 is a novel serogroup of V. cholerae which emerged on the Indian subcontinent in the last few months of 1992 and is the first non-O1 serogroup of V. cholerae to cause epidemic cholera. We have investigated the expression of some of the known virulence factors of classical and El Tor O1 strains of V. cholerae in clinical isolates of O139 strains. We show that, in contrast to other non-O1 strains, O139 strains express TcpA, the major subunit of the toxin-coregulated pilus found in O1 strains. As in O1 strains, the expression of cholera toxin and TcpA is coordinately regulated by environmental parameters in O139 strains. Derivatives of O139 strains that contain a toxR null mutation were constructed and used to demonstrate that the expression of cholera toxin, TcpA, and the outer membrane protein OmpU in O139 strains, as in O1 strains, is dependent on ToxR. Two kinds of evidence suggest that O139 strains are closely related to El Tor strains of V. cholerae. First, both O139 and El Tor strains share a restriction fragment length polymorphism for tcpA, which distinguishes El Tor from classical strains of V. cholerae. Second, cholera toxin production in O139 strains is greatly enhanced by culture conditions that have been previously shown to promote production of cholera toxin in El Tor strains and not in classical strains of V. cholerae. Although O139 is a novel serotype of V. cholerae, O139 strains conform to a fundamental theme that has evolved from the study of O1 strains: ToxR mediates coordinate regulation of virulence gene expression.