Multidrug transporters and antibiotic resistance in Lactococcus lactis.
The Gram-positive bacterium Lactococcus lactis produces two distinct multidrug transporters, designated LmrA and LmrP, that both confer resistance to a wide variety of cationic lipophilic cytotoxic compounds as well as to many clinically relevant antibiotics. While LmrP is a proton/drug antiporter that belongs to the major facilitator superfamily of secondary transporters, LmrA is an ATP-dependent primary transporter that belongs to the ATP-binding cassette superfamily of transport proteins. Both LmrA and LmrP function as "hydrophobic vacuum cleaners" by excreting lipophilic cationic compounds from the inner leaflet of the membrane directly into the external water phase. LmrA is both functionally and structurally homologous to the human multidrug transporter P-glycoprotein. LmrA is a half ABC transporter that is functional as a homodimer, consistent with the general four-domain organization of ABC transporters, and is proposed to mediate drug transport by an alternating two-site transport mechanism.
Department of Microbiology, Groningen Biomolecular Sciences and Biotechnology Institute, University of Groningen, Kerklaan 30, NL-9751 NN Haren, The Netherlands.
Gerrit J
GJ
Poelarends
Piotr
P
Mazurkiewicz
Wil N
WN
Konings
D018528:ATP-Binding Cassette Transporters / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D001426:Bacterial Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D004351:Drug Resistance; D007425:Intracellular Membranes / Q000737:chemistry / Q000378:metabolism; D013294:Lactococcus lactis / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D008051:Lipid Bilayers / Q000737:chemistry; D026901:Membrane Transport Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D008958:Models, Molecular; D027425:ATP-Binding Cassette, Sub-Family C Proteins
D018528:ATP-Binding Cassette Transporters; D001426:Bacterial Proteins; D008051:Lipid Bilayers; D026901:Membrane Transport Proteins; D027425:ATP-Binding Cassette, Sub-Family C Proteins; C101824:LmrA protein, Lactococcus lactis; C096807:LmrP protein, Lactococcus lactis