Genomic epidemiology of Neisseria gonorrhoeae elucidating the gonococcal antimicrobial resistance and lineages/sublineages across Brazil, 2015-16.

Objectives: Neisseria gonorrhoeae antimicrobial resistance (AMR) surveillance is imperative internationally, but only eight (22.9%) countries in the WHO Region of the Americas reported complete AMR data to the WHO Global Gonococcal Antimicrobial Surveillance Program (WHO GASP) in 2016. Genomic studies are ideal for enhanced understanding of gonococcal populations, including the spread of AMR strains. To elucidate the circulating gonococcal Lineages/sublineages, including their AMR determinants, and the baseline genomic diversity among gonococcal strains in Brazil, we conducted WGS on 548 isolates obtained in 2015-16 across all five macroregions in Brazil. Methods: A total of 548 gonococcal isolates cultured across Brazil in 2015-16 were genome sequenced. AMR was determined using agar dilution and/or Etest. Genome sequences of isolates from Argentina (n =158) and the 2016 WHO reference strains (n =14) were included in the analysis. Results: We found 302, 68 and 214 different NG-MAST, MLST and NG-STAR STs, respectively. The phylogenomic analysis identified one main antimicrobial-susceptible Lineage and one AMR Lineage, which was divided into two sublineages with different AMR profiles. Determination of NG-STAR networks of clonal complexes was shown as a new and valuable molecular epidemiological analysis. Several novel mosaic mtrD (and mtrR and mtrE) variants associated with azithromycin resistance were identified. Conclusions: We describe the first genomic baseline data to support the Brazilian GASP. The high prevalence of resistance to ciprofloxacin, tetracycline and benzylpenicillin, and the high number of isolates with mosaic penA and azithromycin resistance mutations, should prompt continued and strengthened AMR surveillance, including WGS, of N. gonorrhoeae in Brazil.