Regulation of cholera toxin production in Vibrio cholerae: genetic analysis of phenotypic instability in hypertoxinogenic mutants.

Hypertoxinogenic mutants of Vibrio cholerae frequently possess mutations in a chromosomal locus called htx. Spontaneously occurring phenotypic revertants were shown to fall into three classes. One class retained the htx mutation and therefore represented a second-site mutation(s) capable of suppressing the Htx phenotype, whereas the other two classes represented strains that had lost the htx mutation. One of the latter two classes appeared to be composed of true genetic revertants, whereas the third class consisted of clones that had replaced htx with a new mutation conferring a hypotoxinogenic phenotype. Several rare N-methyl-N'-nitro-N-nitrosoguanidine-induced hypotoxinogenic mutants selected by rif comutation also map in the same region as htx. This new locus, which mediates the hypotoxinogenic phenotype in these trains and potentially in some hypertoxinogenic phenotypic revertants, has been designated ltx. htx and ltx appear to be regulatory loci, since mutations in both sites alter the level of cholera toxin A and B subunit production coordinately. The genetic data also support a model in which htx- and ltx- are allelic states of the same Tox regulatory locus.