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

Whole genome sequencing of 354 Neisseria gonorrhoeae isolates from the G-ToG trial (2014-2016) reveals that UK gonococcal diversity is structured by sexual network, with MSM-associated lineages showing higher azithromycin and ceftriaxone MICs and enrichment of AMR determinants. This dataset provides a pre-intervention baseline for monitoring the impact of HIV PrEP, Doxy-PEP, and Bexsero vaccination.

Samantha A. McKeand; Michelle Cole; Jeffrey A. Cole; Amanda E. Rossiter-Pearson; Jonathan D. C. Ross; Christoph M. Tang· bioRxiv· 2026· DOI 10.64898/2026.03.20.713202

The core problem

Neisseria gonorrhoeae is 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, the authors analysed whole genome sequences and clinical metadata from 354 isolates collected during the G-ToG clinical trial between 2014 and 2016. The study aims to establish a baseline of gonococcal diversity and AMR prior to 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.

Innovation

The authors performed whole genome sequencing on 354 N. gonorrhoeae isolates from the G-ToG clinical trial, collected between 2014 and 2016. Clinical metadata were integrated with genomic data. Phylogenetic analysis was conducted to assess genetic relatedness and clustering. Minimum inhibitory concentrations (MICs) for azithromycin and ceftriaxone were determined, and the presence of chromosomal AMR determinants and AMR-associated plasmids was assessed. The G-ToG isolates were compared with global datasets to evaluate the breadth of UK gonococcal diversity and potential biases related to participant demographics.

Introduction

Neisseria gonorrhoeae is 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, the authors analysed whole genome sequences and clinical metadata from 354 isolates collected during the G-ToG clinical trial between 2014 and 2016. The study aims to establish a baseline of gonococcal diversity and AMR prior to 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.

Why it matters

These data provide a valuable baseline preceding the implementation of several major UK public health interventions, including HIV PrEP, Doxy-PEP, and vaccination with Bexsero. The strong clustering by sexual network highlights the importance of transmission dynamics in shaping gonococcal populations and AMR. The higher MICs and enrichment of AMR determinants in MSM-associated lineages suggest that this group may be at greater risk of treatment failure and may drive AMR spread. 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.

Who should read this

Praktisi kesehatan, peneliti klinis, dan pembaca Research Digest.

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