title: 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.
authors.affiliation: The University of Birmingham, Edgbaston, Birmingham, B15 2TT, UK.
authors.forename: Anna
authors.initials: A
authors.lastname: Stincone
authors.forename: Nazish
authors.initials: N
authors.lastname: Daudi
authors.forename: Ayesha S
authors.initials: AS
authors.lastname: Rahman
authors.forename: Philipp
authors.initials: P
authors.lastname: Antczak
authors.forename: Ian
authors.initials: I
authors.lastname: Henderson
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Cole
authors.forename: Matthew D
authors.initials: MD
authors.lastname: Johnson
authors.forename: Peter
authors.initials: P
authors.lastname: Lund
authors.forename: Francesco
authors.initials: F
authors.lastname: Falciani
mesh_terms: D000222:Adaptation, Physiological / Q000235:genetics; D001426:Bacterial Proteins / Q000235:genetics / Q000502:physiology; D002473:Cell Wall / Q000378:metabolism; D004734:Energy Metabolism; D004926:Escherichia coli / Q000235:genetics* / Q000378:metabolism; D015964:Gene Expression Regulation, Bacterial; D053263:Gene Regulatory Networks; D006863:Hydrogen-Ion Concentration; D009154:Mutation; D010641:Phenotype; D049490:Systems Biology; D015534:Trans-Activators / Q000235:genetics / Q000502:physiology; D014158:Transcription, Genetic
chemical_list: D001426:Bacterial Proteins; D015534:Trans-Activators; C112177:osmolarity response regulator proteins