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.
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.
Authors: Magnus Unemo; Daniel Golparian; Leonor Sánchez-Busó; Yonatan Grad; Susanne Jacobsson; Makoto Ohnishi; Monica M Lahra; Athena Limnios; Aleksandra E Sikora; Teodora Wi; Simon R Harris Journal: J Antimicrob Chemother Date: 2016-07-17 Impact factor: 5.790
Authors: Chih-Chia Su; Feng Long; Gerry McDermott; William M Shafer; Edward W Yu Journal: Acta Crystallogr Sect F Struct Biol Cryst Commun Date: 2008-03-21
Authors: Fadi E El-Rami; Ryszard A Zielke; Teodora Wi; Aleksandra E Sikora; Magnus Unemo Journal: Mol Cell Proteomics Date: 2018-10-23 Impact factor: 5.911