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  • Whole-genome sequencing reveals transmission of gonococcal antibiotic resistance among men who have sex with men: an observational study

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Basic science
Original article
Whole-genome sequencing reveals transmission of gonococcal antibiotic resistance among men who have sex with men: an observational study
  1. Jason C Kwong1,2,3,
  2. Eric P F Chow4,5,
  3. Kerrie Stevens2,
  4. Timothy P Stinear1,6,
  5. Torsten Seemann1,7,
  6. Christopher K Fairley4,5,
  7. Marcus Y Chen4,5,
  8. Benjamin P Howden1,2,3
  1. 1 Doherty Applied Microbial Genomics, Department of Microbiology and Immunology, The Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, Victoria, Australia
  2. 2 Microbiological Diagnostic Unit Public Health Laboratory, Department of Microbiology and Immunology, The Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, Victoria, Australia
  3. 3 Department of Infectious Diseases, Austin Health, Melbourne, Victoria, Australia
  4. 4 Melbourne Sexual Health Centre, Alfred Health, Carlton, Victoria, Australia
  5. 5 Central Clinical School, Faculty of Medicine, Nursing and Health Sciences, Monash University, Melbourne, Victoria, Australia
  6. 6 Department of Microbiology and Immunology, The Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, Victoria, Australia
  7. 7 Victorian Life Sciences Computation Initiative, University of Melbourne, Melbourne, Victoria, Australia
  1. Correspondence to Professor Benjamin P Howden, Microbiological Diagnostic Unit Public Health Laboratory Peter Doherty Institute for Infection & Immunity, Melbourne, VIC 3000, Australia; bhowden{at}unimelb.edu.au

Abstract

Objectives Drug-resistant Neisseria gonorrhoeae are now a global public health threat. Direct transmission of antibiotic-resistant gonococci between individuals has been proposed as a driver for the increased transmission of resistance, but direct evidence of such transmission is limited. Whole-genome sequencing (WGS) has superior resolution to investigate outbreaks and disease transmission compared with traditional molecular typing methods such as multilocus sequence typing (MLST) and N. gonorrhoeae multiantigen sequence (NG-MAST). We therefore aimed to systematically investigate the transmission of N. gonorrhoeae between men in sexual partnerships using WGS to compare isolates and their resistance to antibiotics at a genome level.

Methods 458 couples from a large prospective cohort of men who have sex with men (MSM) tested for gonorrhoea together between 2005 and 2014 were included, and WGS was conducted on all isolates from couples where both men were culture-positive for N. gonorrhoeae. Resistance-determining sequences were identified from genome assemblies, and comparison of isolates between and within individuals was performed by pairwise single nucleotide polymorphism and pangenome comparisons, and in silico predictions of NG-MAST and MLST.

Results For 33 of 34 (97%; 95% CI 85% to 100%) couples where both partners were positive for gonorrhoea, the resistance-determining genes and mutations were identical in isolates from each partner (94 isolates in total). Resistance determinants in isolates from 23 of 23 (100%; 95% CI 86% to 100%) men with multisite infections were also identical within an individual. These partner and within-host isolates were indistinguishable by NG-MAST, MLST and whole genomic comparisons.

Conclusions These data support the transmission of antibiotic-resistant strains between sexual partners as a key driver of resistance rates in gonorrhoea among MSM. This improved understanding of the transmission dynamics of N. gonorrhoeae between sexual partners will inform treatment and prevention guidelines.

  • gonorrhoea
  • antibiotic resistance
  • modes of transmission

This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/

https://doi.org/10.1136/sextrans-2017-053287

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    Footnotes

    • MYC and BPH contributed equally.

    • Handling editor Catherine A Ison

    • Contributors JCK, EPFC, MYC and BPH designed the study. TS provided analytical tools for genomics analyses. All authors analysed and interpreted the data. JCK primarily drafted the manuscript, with help from MYC and BPH. All authors reviewed and contributed to the final version of the manuscript.

    • Funding This work was supported by the Victorian Government, Australia, through the Microbiological Diagnostic Unit Public Health Laboratory and the Melbourne Sexual Health Centre. JCK (GNT1074824), EPFC (GNT1091226), TPS (GNT1008549) and BPH (GNT1105905) all received funding from the National Health and Medical Research Council of Australia. JCK is also supported by the NHMRC Centre of Research Excellence in Emerging Infectious Diseases (GNT1102962).

    • Competing interests MYC is the principal investigator for a gonorrhoea treatment trial funded by Cempra.

    • Ethics approval Ethics approval was granted by the Alfred Health Human Ethics Committee (approval number 55/15).

    • Provenance and peer review Not commissioned; externally peer reviewed.

    • Data sharing statement Raw sequence data generated for this project have been uploaded to the Sequence Read Archive under the study accession PRJEB17738.