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

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Yahara, Koji, Nakayama, Shu-ichi, Shimuta, Ken, Lee, Ken-ichi, Morita, Masatomo, Kawahata, Takuya, Kuroki, Toshiro, Watanabe, Yuko, Ohya, Hitomi, Yasuda, Mitsuru, Deguchi, Takashi, Didelot, Xavier and Ohnishi, Makoto (2018) Genomic surveillance of Neisseria gonorrhoeae to investigate the distribution and evolution of antimicrobial-resistance determinants and lineages. Microbial Genomics, 4 (8). doi:10.1099/mgen.0.000205

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Official URL: http://dx.doi.org/10.1099/mgen.0.000205

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Abstract

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.

Item Type: Journal Article
Subjects: Q Science > QH Natural history > QH426 Genetics
Q Science > QR Microbiology
R Medicine > RM Therapeutics. Pharmacology
Divisions: Faculty of Science > Life Sciences (2010- )
Library of Congress Subject Headings (LCSH): Neisseria gonorrhoeae -- Genetics, Ceftriaxone, Genomics
Journal or Publication Title: Microbial Genomics
Publisher: Microbiology Society
ISSN: 2057-5858
Official Date: 31 July 2018
Dates:
DateEvent
31 July 2018Available
9 July 2018Accepted
Volume: 4
Number: 8
DOI: 10.1099/mgen.0.000205
Status: Peer Reviewed
Publication Status: Published
Access rights to Published version: Open Access
RIOXX Funder/Project Grant:
Project/Grant IDRIOXX Funder NameFunder ID
JP18fk0108062Japan Agency for Medical Research and Developmenthttp://dx.doi.org/10.13039/100009619
18K17406[MEXT] Ministry of Education, Culture, Sports, Science and Technologyhttp://dx.doi.org/10.13039/501100001700

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