An acid-tolerance response system protecting exponentially growing Escherichia coli

Ying Xu,Jichao Wang,Yamei Ding,Min Liu,Yuhui Wang,Zhe Zhao,Yixin Shi,Shenmei Sun,Bin Liu,Qingsheng Qi,Wenhua Tong,Guang Zhao,Mo Xian

doi:10.1038/s41467-020-15350-5

Abstract

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.

Highlights

The ability to grow at moderate acidic conditions is important to Escherichia coli colonization of the host’s intestine
According to the results shown above, we present a previously uncharacterized acid-tolerance response (ATR) system as well as its regulatory pathway in exponentially growing E. coli
We demonstrated that the two-component system CpxRA can directly sense the acidic environments, and activate transcription of unsaturated fatty acids (UFAs) synthetic genes, resulting in increased UFAs contents in cell membrane lipid and normal growth of E. coli at pH 4.2

Summary

Introduction

The ability to grow at moderate acidic conditions (pH 4.0–5.0) is important to Escherichia coli colonization of the host’s intestine. The ATR system is important for E. coli survival in the mouse intestine and for production of higher level of 3-hydroxypropionate during fermentation. The AR2−AR5 systems are all dependent on a specific extracellular amino acid, and consist of an antiporter as well as a decarboxylase enzyme that is usually induced by low pH and extracellular amino acid[3,7], except that AR2 can be induced at acidic pH in the absence of glutamate[8] They confer acid resistance by consumption of intracellular protons in amino acid decarboxylation reaction to produce a less acidic internal pH, using glutamate, arginine, lysine and ornithine as their corresponding substrates, respectively[1,5,9,10,11,12]. ATR can be activated during adaptation at mild acidic pH by the regulators Fur and PhoPQ in exponential phase cells and by RpoS and OmpR in stationary phase cells, but the stationary phase cells are much more tolerant to acid than the log phase cells[3,4]

Methods

Results

Conclusion