The objective of this study was to estimate the tetracycline resistance level in the modern population of Neisseria gonorrhoeae in the Russian Federation, where this drug was removed from the treatment regimen for gonococcal infections in 2003. A total of 401 isolates collected between 2015 and 2017 were analyzed for genetic markers (chromosomal porB, rpsJ and mtrR gene mutations and the plasmid-located tetM gene) involved in tetracycline resistance. Antibiotic susceptibility testing revealed that 19% of the strains were tetracycline resistant (MIC > 1 mg/L) and that 10% of the strains had intermediate susceptibility (0.5 < MIC ≤ 1 mg/L). Various combinations of mutations identified in the rpsJ (Val57Met/Leu), porB (Gly120Lys/Asp/Asn/Thr and Ala121/Asp/Asn/Gly), and mtrR (-35 del A) genes resulted in MIC increases of up to 1.47 mg/L (geometric mean value). The presence of the tetM gene was detected in 29 strains, including 18 tetM genes of the American type and 11 of the Dutch type. The tetM gene was associated with a strong increase in resistance (MIC > 8 mg/L). One N. gonorrhoeae isolate was found to carry a defective tetM gene with an AG deletion at position 1239-1240, а new stop codon was introduced that caused a defect in TetM protein synthesis and decrease in the tetracycline resistance. Phylogenetic trees constructed using N. gonorrhoeae NG-MAST and tetM loci were compared. Complex relationship was observed between the N. gonorrhoeae sequence type and the tetM plasmid type. Partial recovery of N. gonorrhoeae tetracycline susceptibility was observed relative to the proportion of isolates with resistance detected ten years ago (75%). However, the current levels of tetracycline resistance still preclude the renewed use of these drugs for gonococcal infection therapy.
Keywords: Chromosomal mutations; Genetic determinants of drug resistance; Neisseria gonorrhoeae; Plasmid-based tetM gene, NG-MAST; Tetracycline.
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