A systems biology approach sheds new light on the regulation of acid adaptation in Escherichia coli BW25113 and MG1655 strains

Stincone, Anna (2013). A systems biology approach sheds new light on the regulation of acid adaptation in Escherichia coli BW25113 and MG1655 strains. University of Birmingham. Ph.D.

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Abstract

The ability of Escherichia coli to survive in extreme acid conditions is an important component of its physiology. In my study I have profiled the Escherichia coli K-12 BW25113 strain using microarray technology and I have analysed a multi-omics dataset representing the transcriptional and metabolic responses of the MG1655 Escherichia coli strain. An initial high-level model in the BW25113 strain representing the interaction between two component systems regulators and effectors functions was built using the ARACNE methodology. My model supported the view that acid resistance involves a mechanism based on the transcriptional switch between the expression of genes encoding aerobic and anaerobic enzymes and controlled by the two-component system regulator OmpR. Experimental validation of the model confirmed this hypothesis. This model allowed me to predict that the MG1655 strain would be more sensitive to acid than the related BW25113 strain. Acid exposure induced an opposite response in this strain by repressing most of the anaerobic enzymes in favour of the aerobic metabolism. A dynamical model, developed by using State Space Models, revealed three potential regulators of acid adaptation in the MG1655 strain: OmpR, YehT and DcuR.

I concluded that OmpR has a key role in acid adaptation in both strains and that the ability to reassess the balance in the expression of bioenergetics genes is more important for survival than proton detoxification.

Type of Work:

Thesis (Doctorates > Ph.D.)

Award Type:

Doctorates > Ph.D.

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