INVOLVEMENT OF THE GONOCOCCAL MTRE PROTEIN IN THE RESISTANCE OF NEISSERIA-GONORRHOEAE TO TOXIC HYDROPHOBIC AGENTS

Low-level resistance of Neisseria gonorrhoeae to toxic hydrophobic age nts (HAs), including some antibiotics, is chromosomally mediated via t he multiple transferable resistance (mtr) efflux system. The gene enco ding the 48.3 kDa outer-membrane protein MtrE, which is associated wit h the mtr phenotype, was identified and is homologous to export-associ ated outer-membrane proteins, including the OprM (formerly OprK) lipop rotein of Pseudomonas aeruginosa. Insertional inactivation of the mtrE gene in N. gonorrhoeae strain FA19 resulted in the loss of the outer- membrane protein, with concomitant hypersusceptibility of the mutant s train to a range of HAs. The properties of this mutant confirmed the r ole of MtrE in multidrug resistance mediated by an active efflux mecha nism. Secondary structure predictions for MtrE indicated a largely hyd rophilic protein with a single alpha-helical transmembrane region. A t ransposon-like element, similar to that found downstream of the region containing the promoters for mtrR and mtrC in Neisseria meningitidis, was identified 63 bp downstream of the mtrE gene.