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

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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.