Metagenomic approach to identify agents to restore anti-pseudomonas drugs against multidrug resistant Pseudomonas aeruginosa (MDRP): use of MDRP mutants lacking multidrug efflux pumps.

从高度耐多药的铜绿假单胞菌NCGM2产生的缺乏主要多药外排泵的突变体。代表菌株S1对阿米卡星和环丙沙星有较强的敏感性，但该菌株含有氨基糖苷类6‘-N-乙酰转移酶基因，以及编码DNA旋转酶或拓扑异构酶IV的gyrA、gyrB、parc和pARE基因的典型突变。我们构建了一个从土壤中提取的细菌基因组DNA文库，并试图克隆对该菌株或其缺乏主要多药外排泵的突变株的抗药性抑制剂的DNA，但失败了。然而，我们发现了一种化合物，可以抑制外排介导的阿米卡星对该菌株的耐药性。

A mutant lacking major multidrug efflux pumps derived from highly multidrug resistant Pseudomonas aeruginosa NCGM2. S1, a representative strain of a cluster endemic to Japan showed enhanced suscestibilities to amikacin and ciprofloxacin although the strain harbors an aminoglycoside 6'-N-acetyltransferase gene and the typical mutations within gyrA, gyrB, parC, and parE, which encode DNA gyrase or topoisomerase IV.We constructed a library of bacterial genomic DNA extracted from soils and tried and failed to a clone DNA encodes a drug resistance inhibitor against the strain or its mutants lacking major multidrug efflux pumps. However we discovered a compound that inhibits efflux-mediated amikacin resistance against the strain.