The lactococcal secondary multidrug transporter LmrP confers resistance to lincosamides, macrolides, streptogramins and tetracyclines.
The active efflux of toxic compounds by (multi)drug transporters is one of the mechanisms that bacteria have developed to resist cytotoxic drugs. The authors describe the role of the lactococcal secondary multidrug transporter LmrP in the resistance to a broad range of clinically important antibiotics. Cells expressing LmrP display an increased resistance to the lincosamide, streptogramin, tetracycline and 14- and 15-membered macrolide antibiotics. The streptogramin antibiotic quinupristin, present in the fourth-generation antibiotic RP 59500, can inhibit LmrP-mediated Hoechst 33342 transport, but is not transported by LmrP, indicating that quinupristin acts as a modulator of LmrP activity. LmrP-expressing Lactococcus lactis cells in which a proton-motive force is generated accumulate significantly less tetracycline than control cells without LmrP expression. In contrast, LmrP-expressing and control cells accumulate equal amounts of tetracycline in the absence of metabolic energy. These findings demonstrate that the increased antibiotic resistance in LmrP-expressing cells is a result of the active extrusion of antibiotics from the cell.
Putman
Monique
M
Department of Microbiology, Groningen Biomolecular Sciences and Biotechnology Institute, University of Groningen, Kerklaan 30, 9751 NN Haren, The Netherlands1.
van Veen
Hendrik W
HW
Department of Microbiology, Groningen Biomolecular Sciences and Biotechnology Institute, University of Groningen, Kerklaan 30, 9751 NN Haren, The Netherlands1.
Degener
John E
JE
Department of Medical Microbiology, University of Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands2.
Konings
Wil N
WN
Department of Microbiology, Groningen Biomolecular Sciences and Biotechnology Institute, University of Groningen, Kerklaan 30, 9751 NN Haren, The Netherlands1.
D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics* / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000378:metabolism*; D001693:Biological Transport, Active; D024901:Drug Resistance, Multiple, Bacterial; D013294:Lactococcus lactis / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism; D055231:Lincosamides; D018942:Macrolides; D026901:Membrane Transport Proteins / Q000378:metabolism*; D025361:Streptogramins / Q000493:pharmacokinetics / Q000494:pharmacology; D013754:Tetracyclines / Q000493:pharmacokinetics / Q000494:pharmacology
D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D055231:Lincosamides; C096807:LmrP protein, Lactococcus lactis; D018942:Macrolides; D026901:Membrane Transport Proteins; D025361:Streptogramins; D013754:Tetracyclines