nalB-type mutations causing the overexpression of the MexAB-OprM efflux pump are located in the mexR gene of the Pseudomonas aeruginosa chromosome

Two mutations, one at the nalB and the other at the mexR locus, in the Pseu domonas aeruginosa chromosome are known to cause overexpression of the MexA B-OprM efflux pump. Based on the following results, we concluded that nalB is the mutation that has occurred within the mexR gene of the P. aeruginosa chromosome. (i) Nucleotide sequencing of the mes operon upstream region of 21 independent nalB-type mutants including the original nalB9 revealed tha t all the mutations were located within the mexR gene. The mutations were c lassified into three different groups and nine types including single base substitutions, single base deletions and base insertions. (ii) Substitution of the mutant mexR with the wild-type mexR and replacement of the wild-typ e mexR with a defined mexR mutation resulted in the expression of wild-type and nalB-type MexAB-OprM respectively. which was confirmed by testing the antibiotic susceptibility and P-galactosidase activity of the mexA-lacZ tra nslational fusion. (C) 1999 Federation of European Microbiological Societie s. Published by Elsevier Science B.V. All rights reserved.