A systems biology approach sheds new light on Escherichia coli acid resistance
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AbstractIn 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. © 2011 The Author(s).
CitationStincone, A., Daudi, N., Rahman, A. S., Antczak, P., Henderson, I., Cole, J., Johnson, M. D., Lund, P. and Falciani, F. (2011) A systems biology approach sheds new light on Escherichia coli acid resistance, Nucleic Acids Research, 39(17), pp. 7512–7528.
PublisherOxford University Press (OUP)
JournalNucleic Acids Research
SponsorsBiotechnology and Biological Sciences Research Council (BBSRC) (BBC5151041). A.S. is a recipient of a Darwin Trust of Edinburgh PhD fellowship, N.D. and P.A. are recipients of a BBSRC PhD studentships. Funding for open access charge: BBSRC, UK Research Council.
Except where otherwise noted, this item's license is described as Licence for published version: Creative Commons Attribution-NonCommercial 4.0 International
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