A systems biology approach sheds new light on Escherichia coli acid resistance

Abstract

In order to develop an infection, diarrhogenic Escherichia coli has to pass through the stomach, where the pH can be as low as 1. Mechanisms that enable E. coli to survive in low pH are thus potentially relevant for pathogenicity. Four acid response systems involved in reducing the concentration of intracellular protons have been identified so far. However, it is still unclear to what extent the regulation of other important cellular functions may be required for survival in acid conditions. Here, we have combined molecular and phenotypic analysis of wild-type and mutant strains with computational network inference to identify molecular pathways underlying E. coli response to mild and strong acid conditions. The interpretative model we have developed led to the hypothesis that a complex transcriptional programme, dependent on the two-component system regulator OmpR and involving a switch between aerobic and anaerobic metabolism, may be key for survival. Experimental validation has shown that the OmpR is responsible for controlling a sizeable component of the transcriptional programme to acid exposure. Moreover, we found that a ΔompR strain was unable to mount any transcriptional response to acid exposure and had one of the strongest acid sensitive phenotype observed.

Transcriptomic Analysis of 3-Hydroxypropanoic Acid Stress in Escherichia coli

“…The genes ompR and ompC also have a role in acid tolerance of E. coli. Significant upregulation of ompC has been observed due to acid shock of E. coli [25], while the strong acid sensitivity of E. coli has been reported by deleting ompR [26]. In our experiment, we observed the downregulation of ompF (2.33-fold down), but the transcription of gene ompC (1.01-fold down) was found to be unchanged.…”

Unexpected properties of sRNA promoters allow feedback control via regulation of a two-component system

“…Although the OmpR regulons were found to differ in the two species, with only a few common targets, OmpR controls genes involved in pH homeostasis and acid stress response in both E. coli and Salmonella . In agreement with this, OmpR appears to play an important role in acid resistance (11). At least 4 small RNAs (sRNAs) are also known to be controlled by EnvZ-OmpR: MicC, MicF, OmrA and OmrB (12–14) (see below).…”

Coordinated regulation of acid resistance in Escherichia coli

“…Recently, it was also shown that an OmpR mutant is unable to survive even mild acid stress [71]. OmpR is thought to be regulated by IHF, Crp, and ppGpp.…”