PDF(Pubmed)
Abstract：
An increased efflux activity is one of the major reasons for bacterial antibiotic resistance. The usage of efflux pump inhibitors could be a promising approach to restoring the activity of inefficient antibiotics. The interaction of the RND family efflux pump inhibitor phenylalanyl-arginyl-β-naphthylamide (PAβN) with Salmonella enterica ser. Typhimurium cells was assayed using traditional microbiological techniques and a novel PAβN-selective electrode. Monitoring the PAβN concentration in the medium using the electrode enabled the real-time measurements of this compound\'s interaction with bacterial cells. We showed that S. Typhimurium cells accumulate a high amount of PAβN because of its high affinity to lipopolysaccharides (LPSs), the major constituent of the outer layer of the outer membrane, and does not affect the functioning of the plasma membrane. EDTA enhanced the binding of PAβN to S. Typhimurium cells and the purified E. coli LPSs, but the energization of the cells by glucose does not affect the cell-bound amount of this inhibitor. Polycationic antibiotic Polymyxin B released both the cells accumulated and the suspended LPS-bound PAβN.
摘要：
外排活性增加是细菌抗生素抗性的主要原因之一。外排泵抑制剂的使用可能是恢复低效抗生素活性的有希望的方法。RND家族外排泵抑制剂苯丙氨酰-精氨酰-β-萘酰胺（PAβN）与肠道沙门氏菌的相互作用。使用传统的微生物技术和新型的PAβN选择性电极测定了鼠伤寒杆菌细胞。使用电极监测培养基中的PAβN浓度能够实时测量该化合物与细菌细胞的相互作用。我们表明，鼠伤寒沙门氏菌细胞积累了大量的PAβN，因为它对脂多糖（LPSs）有很高的亲和力，外膜外层的主要成分，并且不影响质膜的功能。EDTA增强了PAβN与鼠伤寒沙门氏菌细胞和纯化的大肠杆菌LPS的结合，但是葡萄糖对细胞的激活并不影响该抑制剂的细胞结合量。聚阳离子抗生素多粘菌素B释放了积累的细胞和悬浮的LPS结合的PAβN。
