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J Infect Dis. 2019 Feb 21. pii: jiz079. doi: 10.1093/infdis/jiz079. [Epub ahead of print]

Evidence of Recent Genomic Evolution in Gonococcal Strains with Decreased Susceptibility to Cephalosporins or Azithromycin in the United States, 2014-2016.

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Division of STD Prevention, Centers for Disease Control and Prevention, Atlanta, Georgia.
Oak Ridge Institute for Science and Education Research Participation and Fellowship Program.
Department of Microbiology and Immunology and The Emory Antibiotic Resistance Center, Emory University School of Medicine, Atlanta, GA.
Laboratories of Bacterial Pathogenesis, Veterans Affairs Medical Center, Decatur, GA.



Given the lack of new antimicrobials or a vaccine, understanding the evolutionary dynamics of Neisseria gonorrhoeae is a significant public and global health priority. We investigated the emergence and spread of gonococcal strains with decreased susceptibility to cephalosporins and azithromycin using detailed genomic analyses of gonococcal isolates collected in the United States from 2014 to 2016.


We sequenced the genomes of 649 isolates collected through the Gonococcal Isolate Surveillance Project (GISP). We examined the genetic relatedness of isolates and assessed associations between clades and various genotypic and phenotypic combinations.


We identified a large and clonal lineage of strains (MLST ST9363) associated with elevated azithromycin MICs (AZI em), characterized by a mosaic mtr locus (C-substitution in the mtrR promoter, mosaic mtrR and mtrD). Mutations in 23S rRNA were sporadically distributed among AZI em strains. Another clonal group (MLST ST1901) possessed seven unique PBP2 patterns, and it shared common mutations in other genes associated with cephalosporin resistance.


Whole genome sequencing methods can enhance monitoring of antimicrobial resistant gonococcal strains by identifying gonococcal populations containing mutations of concern. These methods could inform the development of point-of-care diagnostic tests designed to determine the specific antibiotic susceptibility profile of a gonococcal infection within a patient.


Neisseria gonorrhoeae; antibiotic resistance; cephalosporins; genomic epidemiology; gonorrhea; macrolide


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