Efflux Pump Antibiotic Binding Site Mutations Are Associated with Azithromycin Nonsusceptibility in Clinical Neisseria gonorrhoeae Isolates

摘要

Lyu and Moseng et al. used cryo-electron microscopy to characterize key residuesinvolved in drug binding by mosaic-like MtrD efflux pump alleles in Neisseriagonorrhoeae (1). Isogenic experiments introducing key MtrD substitutions R714G andK823E increased macrolide MICs, leading the authors to predict that nonmosaicMtrD “gonococcal strains bearing both the mtrR promoter and amino acid changesat MtrD positions 714 or 823 could lead to clinically significant levels of Azinonsusceptibility resistance.” We tested this hypothesis by analyzing a globalmeta-analysis collection of 4,852 N. gonorrhoeae genomes (2). In support of theirprediction, we identified clinical isolates with novel nonmosaic MtrD drug bindingsite substitutions across multiple genetic backgrounds associated with elevatedazithromycin MICs (Table 1).