Suppression of the pleiotropic effects of HisH and HisF overproduction identifies four novel loci on the Salmonella typhimurium chromosome: osmH, sfiW, sfiX, and sfiY.

Insertion mutations that suppress some or all the pleiotropic effects of HisH and HisF overproduction were obtained by using transposons Tn10dTet and Tn10dCam. All suppressor mutations proved to be recessive, indicating that their effects were caused by loss of function; thus, the suppressors identify genes that are necessary to trigger the pleiotropic response when HisH and HisF are overproduced. Genetic mapping of the suppressor mutations identifies four novel loci on the Salmonella typhimurium genetic map. Mutations in osmH (min 49) behave as general suppressors that abolish all manifestations of the pleiotropic response. Mutations in sfiY (min 83) suppress cell division inhibition and thermosensitivity but not osmosensitivity. Mutations that suppress only cell division inhibition define another locus, sfiX (min 44). A fourth novel locus, sfiW (min 19), is also involved in cell division inhibition. The phenotype of sfiW mutations is in turn pleiotropic: they suppress cell division inhibition, make S. typhimurium unable to grow in minimal media, and cause slow growth and abnormal colony and cell shape. The inability of sfiW mutants to grow in minimal medium cannot be relieved by any known nutritional requirement or by the use of carbon sources other than glucose. The hierarchy of suppressor phenotypes and the existence of epistatic effects among suppressor mutations suggest a pathway-like model for the Hisc pleiotropic response.