Mutations in trans that affect formate dehydrogenase (fdhF) gene expression in Salmonella typhimurium.

Expression of the fdhF locus of Salmonella typhimurium is shown to be dependent upon ntrA and oxrB. However, the oxrB8 mutation is pleiotropic and also affects the expression of hyd, pepT, and chlC, whereas a mutation in ntrA does not. Insertional inactivation with Tn10 and localized mutagenesis permitted the definition and partial characterization of two new genes, fdhS and fdhR, which appear to be involved in the positive regulation of fdhF expression. Both genes were mapped to the 71- to 72-min region of the S. typhimurium chromosome with the gene order fdhS-crp-fdhR-rpsL. Mutations in fdhS specifically affect fdhF expression without affecting the expression of the other anaerobically induced genes or enzymes that were tested, including hyd, pepT, chlC, nitrite reductase, sulfite reductase, and trimethylamine-N-oxide reductase. Both fdhR and fdhS may be involved in fdhF regulation vis-à-vis oxygen, since localized mutagenesis produced alleles of both genes that permitted the aerobic expression of fdhF. However, fdhR may more directly interact with fdhF, since insertional inactivation of fdhS does not abolish aerobic expression of fdhF in fdhR mutant strains. Taken together, these results suggest that fdhS and fdhR act in concert under anaerobic conditions to activate fdhF transcription.