ATP participates in many cellular metabolic processes as a major substrate to supply energy. Many systems for acidic resistance (AR) under extremely acidic conditions have been reported, but the role of ATP has not been examined. To clarify whether or not ATP is necessary for the AR in Escherichia coli, the AR of mutants deficient in genes for ATP biosynthesis was investigated in this study. The deletion of purA or purB, each of which encodes enzymes to produce AMP from inosinate (IMP), markedly decreased the AR. The content of ATP in these mutants decreased rapidly at pH 2.5 compared to that of the wild type. The AR was again decreased significantly by the mutation of adk, which encoded an enzyme to produce ADP from AMP. The DNA damage in the purA and purB mutants was higher than that in the wild type. These results demonstrated that metabolic processes that require ATP participate in survival under extremely acidic conditions, and that one such system is the ATP-dependent DNA repair system.Since the normal human stomach averages pH 2 for approximately 2 h after it becomes empty, to survive in the mammalian host both commensal and pathogenic enteric bacteria have resistance systems to protect themselves against acidic stress (5,32,36).Four acidic resistance (AR) systems that are induced under different conditions have been proposed for Escherichia coli (5). Acidic resistance system 1 (AR1), which is induced in cells grown to stationary phase in a moderately acidic medium, requires the sigma factor RpoS (3, 27) and the cyclic AMP receptor protein CRP (2). The underlying mechanism remains unclear. The other three systems depend on the presence of specific amino acids. The second AR system (AR2) is a glutamate-dependent system that requires two glutamate decarboxylases (GadA and GadB) and a putative glutamate/␥-aminobutyric acid (GABA) antiporter, GadC (3,8,31). AR3 is an arginine-dependent system. It is induced by low pH under anaerobic conditions, and it requires arginine decarboxylase (AdiA) and arginine/agmatine antiporter (AdiC) (6, 10). AR4 is a lysine-dependent system that requires lysine decarboxylase (CadA) and a lysine/cadaverin antiporter (CadB) (22,40).In addition to these enzymes, multiple global regulators, such as H-NS, CysB, SspA, and HU (1,7,19,34,35), small RNAs (DsrA and GadY) (17, 25), topoisomerase I (37), and Asr (33) have been reported to have some roles in AR, either directly or indirectly. Furthermore, some small molecules, such as indole (9) and CO 2 (38), induced AR. These reports have suggested that multiple metabolic processes besides amino acid decarboxylation are required for survival under acidic conditions.The maintenance of energy is required for many metabolic processes, including the biosynthesis of cellular materials, the membrane transport of ions and organic compounds, DNA repair, cell division and cell motility, and the degradation of macromolecules. E. coli has two major energy sources, ATP and the proton-motive force. The latter is generated via the respiratory chain and i...