Project description

Eszter Lodinsky

AcrAB-TolC is a member of the Resistance-Nodulation-cell Division superfamily of efflux pumps that is notorious for their wide substrate specificity and role in multidrug resistance. The complex harnesses the energy of a proton motive force in order to carry out its function. I aim to elucidate this complex pathway and gain deeper insight into how protonation in the core of the inner membrane leads to the conformational changes required for drug efflux in the periplasmic space. Using a combination of a biochemical and structural approaches, I will look at the phenotypic effects of different mutations and evaluate the underlying structural changes.

Dr. Reinke Müller

I am interested in the determinants of substrate polyspecificity, the investigation of effective inhibition strategies and the the molecular modus operandi of the tripartite model efflux pump AcrAB-TolC from E. coli. In my studies I use methods such as the screening of defined single substitution libraries, phenotypic assays, differential scanning fluorimetry and X-ray crystallography.

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