Acid resistance (AR) is an important mechanism for bacterial survival in extremely acidic environments. Although it has been proposed that pH regulation under acidic conditions is a central mechanism for the induction of AR, it has not been explained to involve pH regulation alone. Recent papers have suggested that amino acids (glutamate, arginine and lysine) and carbon dioxide regulate the AR of Escherichia coli, and that multiple global regulators (RpoS, CRP, H-NS, CysB and SspA), small RNAs (DsrA and GadY), topoisomerase I and many other genes are involved directly or indirectly with AR. It was demonstrated that bacteria also possessed different AR mechanisms in exponential and the stationary growth phase cells. In all cases, the adaptation under weak acidic conditions strengthened the AR. Based on these data, we propose in this review that the AR ability of E. coli is attained by the operation of multiple metabolic processes functioning under acidic conditions, rather than solely by a specific mechanism, such as pH regulation. These multiple processes may cooperate mutually to protect cells against acidic stress.
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