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To counteract the lethal acid stress, bacteria explore such strategies as cytoplasmic decarboxylase‐catalyzed proton consumption and periplasmic chaperone‐assisted protein refolding. Here, we report a periplasmic protease‐mediated acid resistance mechanism in Escherichia coli. Deletion of the protease gene degP dramatically decreases the viability of late log or early stationary phase cells against...