Characterization of the MacA-MacB efflux system in Neisseria gonorrhoeae

Objectives: A homologue of the MacA-MacB ABC transporter of Escherichia coli, which recognizes and exports macrolides, was identified in Neisseria gonorrhoeae. This study was undertaken to determine whether gonococci could use the MacA-MacB homologue to express decreased susceptibility to macrolides. Methods: Techniques of DNA sequencing, gene cloning and expression of recombinant proteins in E. coli, gene mutation construction, transcriptional analysis and antimicrobial susceptibility testing were used in the study. Results: Although the gonococcal MacA-MacB efflux pump enhanced bacterial resistance to macrolides when overexpressed in an E. coli background, its loss in a gonococcal clinical isolate only slightly decreased bacterial resistance to azithromycin and erythromycin. However, a mutation in the -10 sequence of the promoter used in macAB expression enhanced the macrolide resistance of gonococci that produced a defective MtrC-MtrD-MtrE pump, which also recognizes macrolides. Conclusions: The results from this study indicate that gonococci can employ both the MacA-MacB and MtrC-MtrD-MtrE efflux pumps to develop resistance to macrolides, particularly if mutations develop in the promoter that drives transcription of macAB.