Traaseth Group Identifies Key Element in Bacterial Drug Resistance

Traaseth.jpgIn the March 2016 cover article of Nature Chemical Biology, the Traaseth Lab describes the proton-coupled transport mechanism for the Escherichia coli drug efflux pump EmrE using NMR spectroscopy. The group's results show that the global conformational motions necessary for transport are modulated in an allosteric fashion by the protonation state of a membrane-embedded glutamate residue. These observations directly correlate with the resistance phenotype for wild-type and mutant EmrE as a function of pH.  The work is significant because of the critical role drug transporters play in conferring antibiotic and antiseptic resistance.  Anindita Gayen and Maureen Leninger coauthored the study with Prof. Traaseth.

Click here to link to the article, entitled "Protonation of a glutamate residue modulates the dynamics of the drug transporter EmrE," which can be found in Nature Chemical Biology (2016) doi:10.1038/nchembio.1999.
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Abstract: Secondary active transport proteins play a central role in conferring bacterial multidrug resistance. In this work, we investigated the proton-coupled transport mechanism for the Escherichia coli drug efflux pump EmrE using NMR spectroscopy. Our results show that the global conformational motions necessary for transport are modulated in an allosteric fashion by the protonation state of a membrane-embedded glutamate residue. These observations directly correlate with the resistance phenotype for wild-type EmrE and the E14D mutant as a function of pH. Furthermore, our results support a model in which the pH gradient across the inner membrane of E. coli may be used on a mechanistic level to shift the equilibrium of the transporter in favor of an inward-open resting conformation poised for drug binding.
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This research was supported by
the United States National Institutes of Health (NIH).  Maureen Leninger acknowledges support from a Margaret Strauss Kramer Fellowship.





Updated on 05/04/2016