PREVENTION OF DRUG ACCESS TO BACTERIAL TARGETS - PERMEABILITY BARRIERS AND ACTIVE EFFLUX
PREVENTION OF DRUG ACCESS TO BACTERIAL TARGETS - PERMEABILITY BARRIERS AND ACTIVE EFFLUX
复制标题
DOI：
10.1126/science.8153625
复制
发表时间：
1994-04-15
期刊：
影响因子：
56.9
通讯作者：
NIKAIDO, H
中科院分区：
文献类型：
--
作者：
NIKAIDO, H
某些细菌具有低渗透性的膜屏障，因此对许多抗生素具有“内在”抗性;它们在医院环境中存在的众多抗生素中被选择出来，从而导致许多医院获得性感染。一些原本对害虫敏感的物种也可能通过降低膜屏障的渗透性而获得抗性。另一种阻止药物到达靶点的机制是膜相关能量驱动的外排，其在耐药性中起主要作用，特别是与渗透屏障结合时。最近的研究结果表明，存在细菌外流系统的非常广泛的底物特异性，在许多方面让人想起哺乳动物细胞的多药耐药泵。一个这样的系统似乎在铜绿假单胞菌（一种常见的机会致病菌）的内在耐药性中起主要作用。随着制药工业成功地生产出能够克服细菌耐药性的特异性机制的药物，特异性较低的耐药性机制如渗透性屏障和多药主动外排在临床环境中可能变得越来越重要。
Some species of bacteria have low-permeability membrane barriers and are thereby ''intrinsically'' resistant to many antibiotics; they are selected out in the multitude of antibiotics present in the hospital environment and thus cause many hospital-acquired infections. Some strains of originally antibiotic-susceptible species may also acquire resistance through decreases in the permeability of membrane barriers. Another mechanism for preventing access of drugs to targets is the membrane-associated energy-driven efflux, which plays a major role in drug resistance, especially in combination with the permeation barrier. Recent results indicate the existence of bacterial efflux-systems of extremely broad substrate specificity, in many ways reminiscent of the multidrug resistance pump of mammalian cells. One such system seems to play a major role in the intrinsic resistance of Pseudomonas aeruginosa, a common opportunistic pathogen. As the pharmaceutical industry succeeds in producing agents that can overcome specific mechanisms of bacterial resistance, less specific resistance mechanisms such as permeability barriers and multidrug active efflux may become increasingly significant in the clinical setting.