Myristic Acid Inhibits the Activity of the Bacterial ABC Transporter BmrA

Int J Mol Sci. 2021 Dec 17;22(24):13565. 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.

Keywords: ABC transporter; BmrA; inhibitor; membrane transport; myristic acid.

MeSH terms

  • ATP-Binding Cassette Transporters / antagonists & inhibitors*
  • ATP-Binding Cassette Transporters / metabolism
  • Adenosine Triphosphatases / antagonists & inhibitors
  • Adenosine Triphosphatases / metabolism
  • Bacillus subtilis / drug effects*
  • Bacillus subtilis / metabolism
  • Bacterial Proteins / antagonists & inhibitors*
  • Bacterial Proteins / metabolism
  • Drug Discovery
  • Myristic Acid / pharmacology*

Substances

  • ATP-Binding Cassette Transporters
  • Bacterial Proteins
  • Myristic Acid
  • Adenosine Triphosphatases