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Ross, J. D. C.

Publications and source records attributed to Ross, J. D. C..

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↗

Inhibition of Neisseria gonorrhoeae complement-mediated killing during acute gonorrhoea is dependent upon the IgG2:IgG3 antibody ratio

Excessive binding of antibodies to the bacterial cell surface can paradoxically increase resistance of some Gram-negative pathogens to complement-mediated killing (CMK). We examined CMK of 336 Neisseria gonorrhoeae clinical isolates sampled from participants recruited to a clinical trial. Serum bactericidal assays revealed 3% (9/336) of the autologous participant sera that were tested inhibited CMK. Gonococci isolated from these participants were resistant to the autologous host serum, sensitive to a pool of healthy control sera (HCS) and protected by the host serum in a 1:1 mixture with HCS. Analysis of the clinical metadata showed that there were a significantly higher proportion of inhibitory sera found in participants with urethral infections and from men within the transmission network of men who have sex with women (MSW), when compared to the whole cohort. Following antibody purification from selected participants with inhibitory sera (5/9), IgG and IgM protected the autologous isolates from HCS-mediated killing. Only three of these isolates were protected by purified IgA. A closer examination of IgG subclasses using whole gonococcal cell ELISAs revealed a strong correlation between increased IgG2 binding and decreased IgG3 binding to the bacterial cell surface of isolates that were resistant to CMK. This suggests that IgG2 prevents bactericidal IgG3 from initiating CMK and that the IgG2:IgG3 ratio is important for determining either inhibition or killing of isolates. We therefore reveal a previously unreported mechanism by which inhibitory antibodies prevent CMK of N. gonorrhoeae.

microbiology↗