Genomic epidemiology of Neisseria gonorrhoeae elucidating the gonococcal antimicrobial resistance and lineages/sublineages across Brazil, 2015–16
Authors: Golparian Daniel , Bazzo Maria Luiza , Golfetto Lisléia , Gaspar Pamela Cristina , Schörner Marcos André , Schwartz Benzaken Adele , Ramos Mauro Cunha , Ferreira William Antunes , Alonso Neto José Boullosa , Mendes Pereira Gerson Fernando , Unemo Magnus ,   the Brazilian-GASP Network, de Rocco Felipe , Schörner Marcos André , dos Santos Thais Mattos , Martins Jéssica Motta , de Melo Machado Hanalydia , Costa Ligia Maria Bedeschi , Costa Maria Rita Rabelo , de Carvalho Simone Veloso Faria , Dias Luciane Guimarães , de Souza Vasconcelos Waldemara , de Souza Gomes Jairo , de Fátima Pinto da Silva Maria , da Purificação Pereira da Silva Maria , de Matos Rosana Barboza , da Silva Roberto José Carvalho , do Porto Cláudio Campos , da Fonseca Andrade Lidiane , de Fátima Mendes Pereira Lúcia , de Lannoy Leonor Henriette , Eidt Letícia , de Oliveira Arnhold Guilherme Henrique , Muniz Chayane Ariel Souza Coelho , Timm Loeci Natalina , Zoccoli Cassia Maria , Bazzo Maria Luiza , Golfetto Lisléia , Ramos Mauro Cunha , Ferreira William Antunes , de Rocco Felipe , Schörner Marcos André , dos Santos Thais Mattos , Martins Jéssica Motta , de Melo Machado Hanalydia , Costa Ligia Maria Bedeschi , Costa Maria Rita Rabelo , de Carvalho Simone Veloso Faria , Dias Luciane Guimarães , de Souza Vasconcelos Waldemara , de Souza Gomes Jairo , de Fátima Pinto da Silva Maria , da Purificação Pereira da Silva Maria , de Matos Rosana Barboza , da Silva Roberto José Carvalho , do Porto Cláudio Campos , da Fonseca Andrade Lidiane , de Fátima Mendes Pereira Lúcia , de Lannoy Leonor Henriette , Eidt Letícia , de Oliveira Arnhold Guilherme Henrique , Muniz Chayane Ariel Souza Coelho , Timm Loeci Natalina , Zoccoli Cassia Maria , Bazzo Maria Luiza , Golfetto Lisléia , Ramos Mauro Cunha , Ferreira William Antunes 
Published: July 2020

Abstract

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.