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Microb Genom. 2018 Aug;4(8). doi: 10.1099/mgen.0.000205. Epub 2018 Jul 31.

Genomic surveillance of Neisseria gonorrhoeae to investigate the distribution and evolution of antimicrobial-resistance determinants and lineages.

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1​Antimicrobial Resistance Research Center, National Institute of Infectious Diseases, Tokyo, Japan.
2​Department of Bacteriology I, National Institute of Infectious Diseases, Tokyo, Japan.
3​Virology Section, Division of Microbiology, Osaka Institute of Public Health, Osaka, Japan.
4​Department of Microbiology, Kanagawa Prefectural Institute of Public Health, Kanagawa, Japan.
†​Present address: Faculty of Veterinary Medicine, Okayama University of Science, 1-3, Ikoinooka, Imabari, Ehime 794-8555, Japan.
5​Department of Urology, Graduate School of Medicine, Gifu University, Gifu, Japan.
6​Department of Infectious Disease Epidemiology, Imperial College, London, UK.


The first extensively drug resistant (XDR) Neisseria gonorrhoeae strain with high resistance to the extended-spectrum cephalosporin ceftriaxone was identified in 2009 in Japan, but no other strain with this antimicrobial-resistance profile has been reported since. However, surveillance to date has been based on phenotypic methods and sequence typing, not genome sequencing. Therefore, little is known about the local population structure at the genomic level, and how resistance determinants and lineages are distributed and evolve. We analysed the whole-genome sequence data and the antimicrobial-susceptibility testing results of 204 strains sampled in a region where the first XDR ceftriaxone-resistant N. gonorrhoeae was isolated, complemented with 67 additional genomes from other time frames and locations within Japan. Strains resistant to ceftriaxone were not found, but we discovered a sequence type (ST)7363 sub-lineage susceptible to ceftriaxone and cefixime in which the mosaic penA allele responsible for reduced susceptibility had reverted to a susceptible allele by recombination. Approximately 85 % of isolates showed resistance to fluoroquinolones (ciprofloxacin) explained by linked amino acid substitutions at positions 91 and 95 of GyrA with 99 % sensitivity and 100 % specificity. Approximately 10 % showed resistance to macrolides (azithromycin), for which genetic determinants are less clear. Furthermore, we revealed different evolutionary paths of the two major lineages: single acquisition of penA X in the ST7363-associated lineage, followed by multiple independent acquisitions of the penA X and XXXIV in the ST1901-associated lineage. Our study provides a detailed picture of the distribution of resistance determinants and disentangles the evolution of the two major lineages spreading worldwide.


Neisseria gonorrhoeae; antimicrobial resistance; cephalosporin; coalescent; fluoroquinolone; genomic epidemiology; macrolide; phylogeny; recombination; surveillance

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