THE ISOLATION AND CHARACTERIZATION OF MUTANTS ALTERED IN EXPRESSION OF THE HISTIDINE OPERON IN SALMONELLA TYPHIMURIUM

A mutant selection has been performed for the isolation of suppressors of hisT1504, a mutant exhibiting constitutive expression of the histidine operon. By selecting for sensitivity to 3-amino-1,2,4-triazole (AMT), three prototrophic mutants were isolated that were linked to the his operon and reduced for its expression. Two of the mutants, his-4088 and his-4089, are mutated in or near the hisB gene, the structural gene for the target enzyme of AMT, imidazole glycerol phosphate dehydratase. The third mutant, his-4090, represents a novel mutation located near the hisD-hisC intercistronic region. In a hisT background, his-4090 has been found to result in a fifty percent reduction in expression of hisG and hisD, a 30-fold reduction in hisC expression, and a 7-fold reduction in expression of hisB. Although his-4090 is repressible, it behaves as a low level constitutive mutation in response to a variety of genetic and physiological signals. Evidence is presented showing that the slow growth phenotype of his-4090 is reversed by the histidine analogue thiazolealanine, a false feedback inhibitor. Under certain conditions, this mutant has also been found to result in a 3-fold elevation in levels of imidazole, which presumably is due to the accumulation of imidazole acetol phosphate, the substrate for aminotransferase (encoded by the hisC gene). It is proposed that his-4090 represents a mutation in the hisD-hisC intercistronic region that affects the functional integrity of the his polycistronic message