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

Paul, S., Alegre, K. O., Holdsworth, S. R., Rice, M., Brown, J. A., McVeigh, P., Kelly, S. M. and Law, C. J. (2014) A single-component multidrug transporter of the major facilitator superfamily is part of a network that protects Escherichia coli from bile salt stress. Molecular Microbiology, 92(4), pp. 872-884. (doi:10.1111/mmi.12597)

[img]
Preview
Text
94650.pdf - Published Version
Available under License Creative Commons Attribution.

998kB

Publisher's URL: http://dx.doi.org/10.1111/mmi.12597

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.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Kelly, Dr Sharon
Authors: Paul, S., Alegre, K. O., Holdsworth, S. R., Rice, M., Brown, J. A., McVeigh, P., Kelly, S. M., and Law, C. J.
College/School:College of Medical Veterinary and Life Sciences > Institute of Molecular Cell and Systems Biology
Journal Name:Molecular Microbiology
Publisher:Wiley
ISSN:0950-382X
ISSN (Online):1365-2958
Copyright Holders:Copyright © 2014 The Authors
First Published:First published in Molecular Microbiology 92(4):872-884
Publisher Policy:Reproduced under a Creative Commons License

University Staff: Request a correction | Enlighten Editors: Update this record