An ABC-type multidrug transporter of Lactococcus lactis possesses an exceptionally broad substrate specificity.

LmrA is a 590-amino acid membrane protein which confers multidrug resistance on Lactococcus lactis cells by extruding amphiphilic compounds from the inner leaflet of the cytoplasmic membrane at the expense of ATP hydrolysis. Its structural and functional characteristics place it in the P-glycoprotein cluster of the ATP-binding cassette transporter superfamily, making it the first prokaryotic multidrug transporter of this cluster. The number of compounds recognized and transported by LmrA is remarkably vast and includes many lipophilic cations as well as a record of eight classes of clinically relevant broad-spectrum antibiotics. Homologs of LmrA have been found in pathogenic bacteria, suggesting that these putative efflux pumps may play a crucial role in antibiotic resistance of human pathogens. Recent evidence indicates that LmrA is functional as a homodimer, consistent with the overall structure of P-glycoprotein, and mediates drug transport by an alternating two-site transport mechanism. Copyright 2000 Harcourt Publishers Ltd.