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...

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Besides amino acid decarboxylation, the ADP biosynthetic pathway was reported to enhance survival under extremely acidic conditions in Escherichia coli (Sun et al., J. Bacteriol. 193∶ 3072–3077, 2011). E. coli has two pathways for ATP synthesis from ADP: glycolysis and oxidative phosphorylation. We found in this study that the deletion of the F1Fo-ATPase, which catalyzes the synthesis of ATP from ADP and inorganic phosphate using the electro-chemical gradient of protons generated by respiration in E. coli, decreased the survival at pH 2.5. A mutant deficient in hemA encoding the glutamyl tRNA reductase, which synthesizes glutamate 1-semialdehyde also showed the decreased survival of E. coli at pH 2.5. Glutamate 1-semialdehyde is a precursor of heme synthesis that is an essential component of the respiratory chain. The ATP content decreased rapidly at pH 2.5 in these mutants as compared with that of their parent strain. The internal pH was lowered by the deletion of these genes at pH 2.5. These results suggest that respiration and the F1Fo-ATPase are still working at pH 2.5 to enhance the survival under such extremely acidic conditions.

These data indicate that ZOL induces apoptosis or S-phase arrest, both of which are independent of p53 activation and Ras unprenylation, and suggest that ZOL is a possible therapeutic agent to mesothelioma partly through non-Ras- and ERK1/2-mediated pathways.

Aims:  Resistance to acidic stress contributes to bacterial persistence in the host and is thought to promote their passage through the human gastric barrier. The aim of this study was to examine whether nucleosides have a role in the survival under acidic conditions in Escherichia coli. Methods and Results:  We found that adenosine has a function to survive against extremely acidic stress. The deletion of add encoding adenosine deaminase that converts adenosine into inosine and NH3 attenuated the survival in the presence of adenosine. The addition of adenosine increased intracellular pH of E. coli cells in pH 2·5 medium. Addition of inosine or adenine did not increase the resistance to acidic conditions. Conclusions:  Our present results imply that adenosine was used to survive under extremely acidic conditions via the production of NH3. Significance and Impact of the Study:  It has been proposed that amino acid decarboxylation is the major system for the resistance of E. coli to acidic stress. In this study, the adenosine deamination was shown to induce the survival under acidic conditions, demonstrating that bacteria have alternative strategies to survive under acidic conditions besides amino acid decarboxylation.