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The ability to grow at moderate acidic conditions (pH 4.0–5.0) is important to  Escherichia coli  colonization of the host’s intestine. Several regulatory systems are known to control acid resistance in  E. coli , enabling the bacteria to survive under acidic conditions without growth. Here, we characterize an acid-tolerance response (ATR) system and its regulatory circuit, required for  E. coli  exponential growth at pH 4.2. A two-component system CpxRA directly senses acidification through protonation of CpxA periplasmic histidine residues, and upregulates the  fabA  and  fabB  genes, leading to increased production of unsaturated fatty acids. Changes in lipid composition decrease membrane fluidity, F 0 F 1 -ATPase activity, and improve intracellular pH homeostasis. The ATR system is important for  E. coli  survival in the mouse intestine and for production of higher level of 3-hydroxypropionate during fermentation. Furthermore, this ATR system appears to be conserved in other Gram-negative bacteria.

An acid-tolerance response system protecting exponentially growing Escherichia coli