Biochemical Atypia in Russian Neisseria gonorrhoeae Clinical Isolates Belonging to the G807 NG-MAST Genogroup/ST1594 MLST

Abstract

Many current gonococcal clinical isolates in Russia show atypical taxonomically significant biochemical activity, which leads to species misidentification. Molecular typing of such cultures according Neisseria gonorrhoeae multiantigen sequence typing (NG-MAST) and multilocus sequence typing (MLST) protocols assigned them to the G807 NG-MAST GENOGROUP/ST1594 MLST that has been predominant in Russia in recent years. The goal of the study was to analyze the molecular mechanisms of biochemical atypia in N. gonorrhoeae clinical isolates characterized as the members of G807 NG-MAST GENOGROUP/ST1594 MLST. Sixteen isolates of this genogroup were included in the study, eight showed defective amino acid metabolism or loss of D-glucose fermentation. Comparative bioinformatic analysis based on WGS data divided these isolates into two clusters strictly associated with typical or atypical biochemical activity. Cultures with defective amino acid metabolism had a 5-nucleotide insertion in the pip-gene that caused a stop codon and led to synthesis of the non-functional enzyme. Comparison of the sequenced genomes with publicly available N. gonorrhoeae genomes showed the rarity of this insertion. In the global N. gonorrhoeae phylogenetic tree the G807 NG-MAST GENOGROUP/ST1594 MLST forms a distinct branch characterized by 170 SNPs, most of which are non-synonymous. We hypothesized a unique strategy for G807 NG-MAST GENOGROUP/ST1594 MLST clone persistence in the global N. gonorrhoeae population via escape of antimicrobial therapy due to diagnostic misidentification.