Characterization of the MacA-MacB efflux system in Neisseria gonorrhoeae
Corinne E Rouquette-Loughlin1, Jacqueline T Balthazar, William M Shafer
1Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA 30322, USA.
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.
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