We used the technique of Mu d-directed lac operon fusion formation in an effort to identify loci in Salmonella typhimurium which are transcriptionally regulated by nutrient starvation conditions. We identified lacZ operon fusions in eight genetic loci, all of which exhibited increased transcription when starved for two or more of the following nutrients: nicotinate, phosphate, ammonium, glucose, and sulfqte. The loci have been designated stiA to stiH for starvation-inducible loci. Mutations in two sti loci (stiC and stiD) significantly decreased cell viability during prolonged periods of nicotinate starvation. sti4 and stiD are linked and map at 30 min. The stiC, stiE, stiG, and stiH loci mapped at approximately 77, 43, 88, and 56 min, respectively, on the S. typhimurium linkage map.In nature, Salmonella typhimurium can encounter a variety of environmental conditions. Some of these conditions permit optimal or nearly optimal growth, whereas others can cause mild-to-severe metabolic physiological stress, creating feast-or-famine-like situations. It is reasonable to assume that physiological mechanisms have evolved to enable bacteria to survive periods of suboptimal growth conditions or physiological stress. Several different genetic systems which respond to various environmental stresses have been studied in Escherichia coli, including the heat shock regulon (16), the SOS regulon (27), and the phosphate starvation stimulon (28-30).The phosphate starvation stimulon of E. coli appears to be analogous to the system described in this communication for S. typhimurium. Wanner and McSharry (30) identified several genes regulated under phosphate starvation conditions, which were designated psi for phosphate starvation inducible. The psi loci were classified into different genetic and physiological types on the basis of the extent of their regulation by known pho regulatory genes (phoM, phoR, and phoB) (29,30).Since glucose, ammonium, and phosphate are important for NAD biosynthesis and because NAD(P) participates in hundreds of enzymatic reactions (both anabolic and catabolic), it was reasoned that nicotinate (NA) starvation might result in numerous stress signals which, in turn, would trigger the induction of many genes associated with the maintenance or restoration of balanced growth. We report the identification of a system in S. typhimurium which appears to be analogous to the psi system of E. coli (30) but in which the initial selection was for NA starvation-inducible genetic loci. We identified and characterized, using Mu ddirected lac operon fusion construction (1, 2), eight loci which respond to starvation of two or more of the following: NA, phosphate, ammonium, glucose, and sulfate. We refer to the genes which make up this stimulon as sti for starvation inducible. The locus stiA was originally reported as sinA (6). The genetic designation has been changed to avoid potential confusion with a previously used mnemonic. MATERIALS AND METHODSBacterial strains, phage, and transductions. The strains used in this study...