Neisseria gonorrhoeae, the bacterium behind “the clap”, has several tools in its shed to help it evade antibiotics. One such tool is the multidrug efflux pump MtrC-MtrD-MtrE, which shuttles low concentrations of antimicrobials out of the cell before they can take their toxic toll. In mBio this week, researchers describe a single point mutation that enables N. gonorrhoeae to dramatically increase production of this efflux pump without touching the promoters or repressors that normally control its manufacture.
The MtrC-MtrD-MtrE efflux pump is recognizes and exports a broad array of antimicrobials, including macrolide and β-lactam antibiotics, and detergents. In the mBio study, Ohneck et al. examined MS11, a strain of N. gonorrhoeae with a single point mutation 120 base pairs upstream of the genes for the efflux pump. The mutation, which simply traded a T for a C, is located in a non-coding region and not in a promoter or repressor for the efflux pump, but it confers high levels of antimicrobial resistance to MS11 nonetheless. How?
As Ohneck et al. explain, the sequence created by the mutation acts as a second, stronger transcription promoter for MtrC-MtrD-MtrE that results in a substantial increase in resistance to antimicrobials. The numerous efflux pumps even export antimicrobial factors the host makes to get rid of infection, like antimicrobial peptide LL-37, an ability that may make explain why strains with the point mutation are more infectious than other strains. What’s more, the mutation does not disrupt any other components of the efflux system, including the activator and the repressor, which are global regulators in N. gonorrhoeae and control a multitude of other genes. This ability to increase production of MtrC-MtrD-MtrE without affecting the regulation of other genes needed for infection and survival represents a highly efficient and minimally disruptive mechanism of developing antimicrobial resistance. A win-win for N. gonorrhoeae. The authors say they will follow up on this study with sequence analysis of the promoter regions of other efflux pumps, both in Neisseria and in other pathogenic organisms, to determine if this mechanism is widely used among pathogens or is unique to N. gonorrhoeae and MtrC-MtrD-MtrE.