Genomic epidemiology of <i>Neisseria gonorrhoeae</i> isolates from the G-ToG clinical trial, 2014-2016

ABSTRACT Neisseria gonorrhoeae remains a major public health threat due to rising incidence and increasing antimicrobial resistance (AMR). To characterise the landscape of gonococci circulating in England a decade ago, we analysed whole genome sequences and clinical metadata from 354 isolates collected during the G-ToG clinical trial between 2014 and 2016. Comparison with global datasets demonstrated that the G-ToG isolates captured the breadth of UK gonococcal diversity, mapping across multiple lineages without evidence of marked bias related to participant demographic characteristics. The phylogenetic structure of gonococcal isolates within the collection was strongly shaped by sexual network, with statistically significant clustering of isolates circulating within heterosexual individuals compared with the men who have sex with men (MSM) transmission group. MSM-associated lineages exhibited higher minimum inhibitory concentration (MICs) to azithromycin and ceftriaxone and were enriched for corresponding chromosomal AMR determinants and AMR-associated plasmids. These data provide a valuable baseline preceding the implementation of several major UK public health interventions, including HIV pre-exposure prophylaxis (HIV PrEP), doxycycline post-exposure prophylaxis (Doxy-PEP) and vaccination with Bexsero. Continued integration of genomic and epidemiological surveillance will be essential to monitor whether these interventions reshape gonococcal transmission dynamics and AMR trajectories, guiding future control strategies.