RRC ID 35662
Author Paul S, Alegre KO, Holdsworth SR, Rice M, Brown JA, McVeigh P, Kelly SM, Law CJ.
Title A single-component multidrug transporter of the major facilitator superfamily is part of a network that protects Escherichia coli from bile salt stress.
Journal Mol Microbiol
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.
Volume 92(4)
Pages 872-84
Published 2014-5-1
DOI 10.1111/mmi.12597
PMID 24684269
PMC PMC4235344
MeSH Antiporters / metabolism* Bacterial Outer Membrane Proteins / metabolism Bile Acids and Salts / metabolism* Bile Acids and Salts / toxicity* Drug Tolerance* Escherichia coli / drug effects* Escherichia coli / metabolism* Escherichia coli Proteins / metabolism* Lipoproteins / metabolism Membrane Transport Proteins / metabolism Multidrug Resistance-Associated Proteins / metabolism
IF 3.418
Times Cited 25
Prokaryotes E. coli ME9062(BW25113) Keio collection