Putman Monique, van Veen Hendrik W, Degener John E, Konings Wil N
Department of Microbiology, Groningen Biomolecular Sciences and Biotechnology Institute, University of Groningen, Kerklaan 30, 9751 NN Haren, The Netherlands1.
Department of Medical Microbiology, University of Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands2.
Microbiology (Reading). 2001 Oct;147(Pt 10):2873-2880. doi: 10.1099/00221287-147-10-2873.
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.
（多）药转运蛋白对有毒化合物的主动外排是细菌发展出的抵抗细胞毒性药物的机制之一。作者描述了乳球菌次级多药转运蛋白LmrP在对多种临床上重要抗生素的耐药性中的作用。表达LmrP的细胞对林可酰胺类、链阳菌素类、四环素类以及14和15元大环内酯类抗生素表现出增强的耐药性。存在于第四代抗生素RP 59500中的链阳菌素类抗生素奎奴普丁可抑制LmrP介导的Hoechst 33342转运，但不被LmrP转运，这表明奎奴普丁作为LmrP活性的调节剂。产生质子动力的表达LmrP的乳酸乳球菌细胞积累的四环素明显少于不表达LmrP的对照细胞。相反，在没有代谢能量的情况下，表达LmrP的细胞和对照细胞积累等量的四环素。这些发现表明，表达LmrP的细胞中抗生素耐药性增强是抗生素从细胞中主动排出的结果。
