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 resistanc e on Lactococcus lactis cells by extruding amphiphilic compounds from the i nner leaflet of the cytoplasmic membrane at the expense of ATP hydrolysis. Its structural and functional characteristics place it in the P-glycoprotei n cluster of the ATP-binding cassette transporter superfamily, making it th e first prokaryotic multidrug transporter of this cluster. The number of co mpounds 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 pa thogenic bacteria, suggesting that these putative efflux pumps may play a c rucial role in antibiotic resistance of human pathogens. Recent evidence in dicates 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. (C) 2000 Harcourt Publishers Ltd.