Emergence and evolution of antimicrobial resistance genes and mutations in Neisseria gonorrhoeae

Genome Medicine

Koji Yahara¹  Aki Hirabayashi¹  Masato Suzuki¹  Ken Shimuta²  Mitsuru Yasuda³  Shu-ichi Nakayama⁴  Makoto Ohnishi⁴  Yonatan H. Grad⁵  Kevin C. Ma⁵  Tatum D. Mortimer⁵  Michio Jinnai⁶  Yuko Watanabe⁶  Hitomi Ohya⁶  Toshiro Kuroki⁷  Takashi Deguchi⁸  Martin C. J. Maiden⁹  Odile B. Harrison⁹  Vegard Eldholm^1,10 

[1] Antimicrobial Resistance Research Center, National Institute of Infectious Diseases, Tokyo, Japan;Antimicrobial Resistance Research Center, National Institute of Infectious Diseases, Tokyo, Japan;Department of Bacteriology I, National Institute of Infectious Diseases, Tokyo, Japan;Center for Nutrition Support and Infection Control, Gifu University Hospital, Gifu, Japan;Department of Bacteriology I, National Institute of Infectious Diseases, Tokyo, Japan;Department of Immunology and Infectious Diseases, Harvard T. H. Chan School of Public Health, Boston, MA, USA;Department of Microbiology, Kanagawa Prefectural Institute of Public Health, Chigasaki, Kanagawa, Japan;Department of Microbiology, Kanagawa Prefectural Institute of Public Health, Chigasaki, Kanagawa, Japan;Present address: Faculty of Veterinary Medicine, Okayama University of Science, 1-3 Ikoinooka, 794-8555, Imabari, Ehime, Japan;Department of Urology, Kizawa Memorial Hospital, Gifu, Japan;Department of Zoology, University of Oxford, Oxford, UK;Division of Infection Control and Environmental Health, Norwegian Institute of Public Health, Oslo, Norway;

关键词: Recombination;    Horizontal gene transfer;    Genomic epidemiology;    Antimicrobial resistance;    Phylogeny;    Surveillance;    Evolution;    Neisseria gonorrhoeae;   

DOI  :  10.1186/s13073-021-00860-8

来源: Springer

【 摘 要 】

BackgroundAntimicrobial resistance in Neisseria gonorrhoeae is a global health concern. Strains from two internationally circulating sequence types, ST-7363 and ST-1901, have acquired resistance to third-generation cephalosporins, mainly due to mosaic penA alleles. These two STs were first detected in Japan; however, the timeline, mechanism, and process of emergence and spread of these mosaic penA alleles to other countries remain unknown.MethodsWe studied the evolution of penA alleles by obtaining the complete genomes from three Japanese ST-1901 clinical isolates harboring mosaic penA allele 34 (penA-34) dating from 2005 and generating a phylogenetic representation of 1075 strains sampled from 35 countries. We also sequenced the genomes of 103 Japanese ST-7363 N. gonorrhoeae isolates from 1996 to 2005 and reconstructed a phylogeny including 88 previously sequenced genomes.ResultsBased on an estimate of the time-of-emergence of ST-1901 (harboring mosaic penA-34) and ST-7363 (harboring mosaic penA-10), and > 300 additional genome sequences of Japanese strains representing multiple STs isolated in 1996–2015, we suggest that penA-34 in ST-1901 was generated from penA-10 via recombination with another Neisseria species, followed by recombination with a gonococcal strain harboring wildtype penA-1. Following the acquisition of penA-10 in ST-7363, a dominant sub-lineage rapidly acquired fluoroquinolone resistance mutations at GyrA 95 and ParC 87-88, by independent mutations rather than horizontal gene transfer. Data in the literature suggest that the emergence of these resistance determinants may reflect selection from the standard treatment regimens in Japan at that time.ConclusionsOur findings highlight how antibiotic use and recombination across and within Neisseria species intersect in driving the emergence and spread of drug-resistant gonorrhea.

【 授权许可】

CC BY