Myristic Acid Inhibits the Activity of the Bacterial ABC Transporter BmrA.

Kristin Oepen,Eckhard Thines,Johannes C Liermann,Dirk Schneider,Hüseyin Özbek,Anja Schüffler

doi:10.3390/ijms222413565

Abstract

ATP-binding cassette (ABC) transporters are conserved in all kingdoms of life, where they transport substrates against a concentration gradient across membranes. Some ABC transporters are known to cause multidrug resistances in humans and are able to transport chemotherapeutics across cellular membranes. Similarly, BmrA, the ABC transporter of Bacillus subtilis, is involved in excretion of certain antibiotics out of bacterial cells. Screening of extract libraries isolated from fungi revealed that the C14 fatty acid myristic acid has an inhibitory effect on the BmrA ATPase as well as the transport activity. Thus, a natural membrane constituent inhibits the BmrA activity, a finding with physiological consequences as to the activity and regulation of ABC transporter activities in biological membranes.

Highlights

Membrane integral transport proteins mediate and control the translocation of essential compounds across biological membranes, involving the uptake and efflux of sugars, inorganic ions, nucleotides or drugs [1]
Primary active transporters use the energy gained via ATP hydrolysis for transport [1,2], and such transport ATPases are typically represented by ion pumps and ATP-binding cassette (ABC) transporters [2]
All ABC transporters consist of two nucleotide binding domains (NBDs) and two transmembrane domains (TMDs)

Summary

Introduction

Membrane integral transport proteins mediate and control the translocation of essential compounds across biological membranes, involving the uptake and efflux of sugars, inorganic ions, nucleotides or drugs [1]. Primary active transporters use the energy gained via ATP hydrolysis for transport [1,2], and such transport ATPases are typically represented by ion pumps and ATP-binding cassette (ABC) transporters [2]. ABC transporters can be found in all kingdoms of life and they either import or export substrates against a concentration gradient. In bacteria, ABC importers and exporters can be found, eukaryotes mainly contain exporters [1,3]. All ABC transporters consist of two nucleotide binding domains (NBDs) and two transmembrane domains (TMDs).

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