Background: Helicobacter pylori colonizes the acid environment of the gastric mucosa. Like other enteric bacterial pathogens, including Salmonella enterica, which must survive a brief exposure to that environment, H. pylori displays a rapid response to subtle changes in pH, which confers an increased ability to survive at more extreme acidic pH. This two-step acid tolerance response (ATR) requires de novo protein synthesis and is dependent on the function of the global regulatory protein Fur. Objective: We have explored the physiological bases of the ATR in H. pylori. Materials and Methods: Proteomic analysis of phenotypes of H. pylori and fur mutant strains show that subtle pH changes elicit significant changes in the pattern of proteins synthesized. Results: A loss-of-function mutation in the fur gene, obtained by insertion of an antibiotic resistance cassette, indicated that Fur regulates the expression of a fraction of H. pylori proteins. Conclusion: A subset of proteins is involve