An acid-tolerance response system protecting exponentially growing Escherichia coli

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, F0F1-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. The ability to grow at acidic pH is crucial for E. coli colonization of the host's intestine. Here, the authors identify an acid-tolerance response system that is important for E. coli exponential growth at pH 4.2, survival in the mouse intestine, and production of 3-hydroxypropionate during fermentation.