烷基氨基喹啉可抑制多重耐药临床分离株中的细菌抗生素外排泵。
Alkylaminoquinolines inhibit the bacterial antibiotic efflux pump in multidrug-resistant clinical isolates.
作者信息
Malléa Monique, Mahamoud Abdallah, Chevalier Jacqueline, Alibert-Franco Sandrine, Brouant Pierre, Barbe Jacques, Pagès Jean-Marie
机构信息
EA2197, IFR48, Faculté de Médecine, Université de la Méditerranée, 27 Boulevard Jean Moulin, 13385 Marseille Cedex 05, France.
出版信息
Biochem J. 2003 Dec 15;376(Pt 3):801-5. doi: 10.1042/BJ20030963.
Over the last decade, MDR (multidrug resistance) has increased worldwide in microbial pathogens by efflux mechanisms, leading to treatment failures in human infections. Several Gram-negative bacteria efflux pumps have been described. These proteinaceous channels are capable of expelling structurally different drugs across the envelope and conferring antibiotic resistance in various bacterial pathogens. Combating antibiotic resistance is an urgency and the blocking of efflux pumps is an attractive response to the emergence of MDR phenotypes in infectious bacteria. In the present study, various alkylaminoquinolines were tested as potential inhibitors of drug transporters. We showed that alkylaminoquinolines are capable of restoring susceptibilities to structurally unrelated antibiotics in clinical isolates of MDR Gram-negative bacteria. Antibiotic efflux studies indicated that 7-nitro-8-methyl-4-[2'-(piperidino)ethyl]aminoquinoline acts as an inhibitor of the AcrAB-TolC efflux pump and restores a high level of intracellular drug concentration. Inhibitory activity of this alkylaminoquinoline is observed on clinical isolates showing different resistance phenotypes.
在过去十年中,微生物病原体中的多药耐药性(MDR)通过外排机制在全球范围内有所增加,导致人类感染治疗失败。已经描述了几种革兰氏阴性菌外排泵。这些蛋白质通道能够将结构不同的药物排出包膜,并在各种细菌病原体中赋予抗生素抗性。对抗抗生素耐药性迫在眉睫,而阻断外排泵是应对感染性细菌中MDR表型出现的一种有吸引力的对策。在本研究中,测试了各种烷基氨基喹啉作为药物转运蛋白的潜在抑制剂。我们表明,烷基氨基喹啉能够恢复MDR革兰氏阴性菌临床分离株对结构不相关抗生素的敏感性。抗生素外排研究表明,7-硝基-8-甲基-4-[2'-(哌啶基)乙基]氨基喹啉作为AcrAB-TolC外排泵的抑制剂,可恢复高水平的细胞内药物浓度。在显示不同耐药表型的临床分离株上观察到这种烷基氨基喹啉的抑制活性。