Adaptive Acid Tolerance Response of Salmonella typhimurium Salmonella endure intervals of acid stress in widely diverse environments ranging from pond water to fused phagolysosomes infected macrophages. This research investigates a newly discovered adaptive response which contributes to survival of these bacteria in acid environments. The acidification tolerance response (ATR) is induced when cells are shifted from pH 7.4 to pH 5.8 for one doubling. Subsequent exposure of the adapted cells and unadapted cells to pH 3.3 results in a rapid, logarithmic death of the unadapted cells but marked survival of adapted cells. This research investigates the ATR phenomenon at the biochemical, genetic and molecular levels. Experiments include measuring the internal pH, buffering capacity, proton influx and proton efflux of pH 5.8 adapted vs. unadapted cells and examining polypeptides produced during adaptation. To initiate the genetic studies, a series of selective procedures have been developed to screen for ATR-related acid-resistant and supersensitive mutants. Each mutant gene must affect adaptive acid tolerance, alter the expression of specific ATR polypeptides and be defective in the adaptive acid tolerance mechanism(s) identified during the biochemical investigations.%%% This system of adaptive acid tolerance is most certainly of major importance to Salmonella in surviving acid environments both in nature and in an infected host. The multifaceted study presented here will open exciting new areas of research into how other organisms, both prokaryotic and eukaryotic, handle acid stress.***//