Competitive growth advantage of nontoxigenic mutants in the stationary phase in archival cultures of pathogenic Vibrio cholerae strains.

Spontaneous nontoxigenic mutants of highly pathogenic Vibrio cholerae O1 strains accumulate in large numbers during long-term storage of the cultures in agar stabs. In these mutants, production of the transcriptional regulator ToxR was reduced due to the presence of a mutation in the ribosome-binding site immediately upstream of the toxR open reading frame. Consequently, the ToxR-dependent virulence regulon was turned off, with concomitant reduction in the expression of cholera toxin and toxin-coregulated pilus. An intriguing feature of these mutants is that they have a competitive fitness advantage when grown in competition with the parent strains in stationary-phase cocultures which is independent of RpoS, the only locus known to be primarily associated with acquisition of a growth advantage phenotype in bacteria.