The lactococcal secondary multidrug transporter LmrP confers resistance tolincosamides, 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 transporte r LmrP in the resistance to a broad range of clinically important antibioti cs. Cells expressing LmrP display an increased resistance to the lincosamid e, streptogramin, tetracycline and 14- and 15-membered macrolide antibiotic s. The streptogramin antibiotic quinupristin, present in the fourth-generat ion antibiotic RP 59500, can inhibit LmrP-mediated Hoechst 33342 transport, but is not transported by LmrP, indicating that quinupristin acts as a mod ulator of LmrP activity. LmrP-expressing Lactococcus lactis cells in which a protonmotive force is generated accumulate significantly less tetracyclin e than control cells without LmrP expression. In contrast, LmrP-expressing and control cells accumulate equal amounts of tetracycline in the absence o f metabolic energy. These findings demonstrate that the increased antibioti c resistance in LmrP-expressing cells is a result of the active extrusion o f antibiotics from the cell.