Abstract

Comparative whole-genome analysis was performed for Neisseria gonorrhoeae isolates belonging to the Neisseria gonorrhoeae multiantigen sequence typing (NG-MAST) types predominant worldwide — 225, 1407, 2400, 2992, and 4186 — and to genogroup 807, the most common genogroup in the Russian Federation. Here, for the first time, the complete genomes of 25 N. gonorrhoeae isolates from genogroup 807 were obtained. For NG-MAST types 225, 1407, 2400, 2992, and 4186, genomes from the Pathogenwatch database were used. The phylogenetic network constructed for 150 genomes showed that the clustering according to NG-MAST type corresponded to the clustering according to genome. Comparisons of genomes of the six sequence types revealed 8-20 genes specific to each sequence type, including the loci for phase variations and genetic components of the gonococcal genetic island (GGI). NG-MAST type 2992 and 4186 isolates either lacked the GGI or carried critical mutations in genes essential for DNA secretion. In all analyzed genogroup 807 isolates, substitution of the essential atlA gene with the eppA gene was found, accompanied by a change in the traG allele, replacement of the ych gene with ych1, and the absence of the exp1 gene, which is likely to result in loss of GGI functionality. For the NG-MAST type 225, 1407 and 2400 isolates, no premature stop codons or reading frameshifts were found in the genes essential for GGI function. A relationship between isolate susceptibility to ciprofloxacin, penicillin, tetracycline and the presence of lesions in GGI genes necessary for DNA secretion was established. The N. gonorrhoeae evolutionary pathways, which allow a particular sequence type to maintain long-term predominance in the population, may include changes in genes responsible for adhesion and virulence, changes in the GGI structure, preservation of genes carrying drug resistance determinants, and changes in genes associated with host adaptation or encoding enzymes of biochemical pathways.

Highlights

  • Gonococcal infection caused by Neisseria gonorrhoeae is one of the most common sexually transmitted diseases

  • As seen in the figure, the clustering of isolates according to Neisseria gonorrhoeae multiantigen sequence typing (NG-MAST) type corresponded to clustering according to the core genomes of N. gonorrhoeae sequence types (STs)

  • The complete genomes of 25 Russian isolates belonging to ST 807 and closely related STs were obtained for the first time

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Summary

Introduction

Gonococcal infection caused by Neisseria gonorrhoeae is one of the most common sexually transmitted diseases. The Neisseria gonorrhoeae multiantigen sequence typing (NG-MAST) scheme is a traditional tool for studying the molecular epidemiology of gonococcal infection (ECDC report, 2018). This method allows one to perform two related challenging endeavors: first, to isolate a meaningful number of genetic variants [sequence types (STs)] within the N. gonorrhoeae species and, on this basis, to analyze the transmission routes of gonococcal infection (Martin et al, 2004); second, to identify and control the spread of the most epidemiologically dangerous clones with multiple resistance to antimicrobial drugs (Chisholm et al, 2013). WGS data have been successfully used to identify the determinants of resistance in multiresistant isolates from Europe (Jacobsson et al, 2016; Abrams and Trees, 2017; Harris et al, 2018; Ryan et al, 2018) and the USA (Grad et al, 2016); to study phylogenetic relationships, population structure and molecular epidemiology (Demczuk et al, 2015; Ezewudo et al, 2015; Grad et al, 2016; Abrams and Trees, 2017; Ryan et al, 2018; Harrison et al, 2020); and to predict the level of resistance to various drugs (Eyre et al, 2017; Golparian et al, 2018)

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