bioRxiv Science⌕ Search

Biology subjects

Cole, M. J.

Publications and source records attributed to Cole, M. J..

2 recordsLinked to original sources

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

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.

genomics↗

A community-driven resource for genomic surveillance of Neisseria gonorrhoeae at Pathogenwatch

BackgroundAntimicrobial resistant (AMR) Neisseria gonorrhoeae is an urgent threat to public health, as strains resistant to at least one of the two last line antibiotics used in empiric therapy of gonorrhoea, ceftriaxone and azithromycin, have spread internationally. Whole genome sequencing (WGS) data can be used to identify new AMR clones, transmission networks and inform the development of point-of-care tests for antimicrobial susceptibility, novel antimicrobials and vaccines. Community driven tools that provide an easy access to and analysis of genomic and epidemiological data is the way forward for public health surveillance. MethodsHere we present a public health focussed scheme for genomic epidemiology of N. gonorrhoeae at Pathogenwatch (https://pathogen.watch/ngonorrhoeae). An international advisory group of experts in epidemiology, public health, genetics and genomics of N. gonorrhoeae was convened to inform on the utility of current and future analytics in the platform. We implement backwards compatibility with MLST, NG-MAST and NG-STAR typing schemes as well as an exhaustive library of genetic AMR determinants linked to a genotypic prediction of resistance to eight antibiotics. A collection of over 12,000 N. gonorrhoeae genome sequences from public archives has been quality-checked, assembled and made public together with available metadata for contextualization. ResultsAMR prediction from genome data revealed specificity values over 99% for azithromycin, ciprofloxacin and ceftriaxone and sensitivity values around 99% for benzylpenicillin and tetracycline. A case study using the Pathogenwatch collection of N. gonorrhoeae public genomes showed the global expansion of an azithromycin resistant lineage carrying a mosaic mtr over at least the last 10 years, emphasizing the power of Pathogenwatch to explore and evaluate genomic epidemiology questions of public health concern. ConclusionsThe N. gonorrhoeae scheme in Pathogenwatch provides customized bioinformatic pipelines guided by expert opinion that can be adapted to public health agencies and departments with little expertise in bioinformatics and lower resourced settings with internet connection but limited computational infrastructure. The advisory group will assess and identify ongoing public health needs in the field of gonorrhoea, particularly regarding gonococcal AMR, in order to further enhance utility with modified or new analytic methods.

genomics↗