A single-component multidrug transporter of the major facilitator superfamily is part of a network that protects Escherichia coli from bile salt stress

Stephanie Paul, Kamela O. Alegre, Scarlett R. Holdsworth, Matthew Rice, James A. Brown, Paul McVeigh, Sharon M. Kelly, Christopher J. Law

Research output: Contribution to journalArticle

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Abstract

Resistance to high concentrations of bile salts in the human intestinal tract is vital for the survival of enteric bacteria such as Escherichia coli. Although the tripartite AcrAB-TolC efflux system plays a significant role in this resistance, it is purported that other efflux pumps must also be involved. We provide evidence from a comprehensive suite of experiments performed at two different pH values (7.2 and 6.0) that reflect pH conditions that E. coli may encounter in human gut that MdtM, a single-component multidrug resistance transporter of the major facilitator superfamily, functions in bile salt resistance in E. coli by catalysing secondary active transport of bile salts out of the cell cytoplasm. Furthermore, assays performed on a chromosomal ΔacrB mutant transformed with multicopy plasmid encoding MdtM suggested a functional synergism between the single-component MdtM transporter and the tripartite AcrAB-TolC system that results in a multiplicative effect on resistance. Substrate binding experiments performed on purified MdtM demonstrated that the transporter binds to cholate and deoxycholate with micromolar affinity, and transport assays performed on inverted vesicles confirmed the capacity of MdtM to catalyse electrogenic bile salt/H(+) antiport.
Original languageEnglish
Pages (from-to)872-884
Number of pages13
JournalMolecular Microbiology
Volume92
Issue number4
Early online date13 Apr 2014
DOIs
Publication statusPublished - May 2014

Bibliographical note

© 2014 The Authors. Molecular Microbiology published by John Wiley & Sons Ltd.

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