Resistance of Neisseria gonorrhoeae isolates to beta-lactam antibiotics (benzylpenicillin and ceftriaxone) in Russia, 2015-2017

• Published in: PloS one 2019-07, Vol.14 (7), p.e0220339-e0220339
• Main Authors: Shaskolskiy, Boris, Dementieva, Ekaterina, Kandinov, Ilya, Filippova, Marina, Petrova, Natalia, Plakhova, Xenia, Chestkov, Alexander, Kubanov, Alexey, Deryabin, Dmitry, Gryadunov, Dmitry
• Format: Article
• Language: English
• Subjects: Adult; Amides; Amino Acid Substitution - genetics; Amino acids; Anti-Bacterial Agents - pharmacology; Anti-Bacterial Agents - therapeutic use; Antibiotics; Antiinfectives and antibacterials; Antimicrobial agents; Antimicrobial resistance; Benzylpenicillin; Beta lactam antibiotics; Beta lactamases; beta-Lactam Resistance - drug effects; beta-Lactam Resistance - genetics; beta-Lactamases - genetics; Biology and Life Sciences; Ceftriaxone; Ceftriaxone - pharmacology; Ceftriaxone - therapeutic use; Cephalosporins; Clinical isolates; Cosmetology; Deoxyribonucleic acid; Dilution; Distribution; DNA; DNA chips; DNA microarrays; DNA Mutational Analysis; DNA sequencing; Dosage and administration; Drug resistance; Drug Resistance, Bacterial - drug effects; Drug Resistance, Bacterial - genetics; Drug therapy; Efflux; Female; Gene mutation; Gene sequencing; Genes; Gonorrhea; Gonorrhea - drug therapy; Gonorrhea - epidemiology; Gonorrhea - microbiology; Humans; Laboratories; Lactams; Male; Medicine and Health Sciences; Microbial drug resistance; Microbial Sensitivity Tests; Mitochondrial DNA; Molecular biology; Mutation; Neisseria gonorrhoeae - drug effects; Neisseria gonorrhoeae - genetics; Neisseria gonorrhoeae - isolation & purification; Neisseria infections; Penicillin; Penicillin G; Penicillin G - pharmacology; Penicillin G - therapeutic use; Penicillins; People and Places; Plasmids; Polymorphism, Genetic; Prevention; Proteins; Russia - epidemiology; Surveillance; Tetracyclines; β Lactamase; β-Lactam antibiotics
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0220339

The goal of this work was to study the phenotypic susceptibility and resistance determinants of N. gonorrhoeae isolates to beta-lactam antimicrobials (benzylpenicillin and ceftriaxone). A total of 522 clinical isolates collected in Russia in 2015-2017 were analysed for susceptibility using the agar dilution method. DNA loci involved in antimicrobial resistance were identified using DNA microarray analysis and sequencing. Resistance to benzylpenicillin remained high, with 7.7% of isolates resistant (MICpen > 1 mg/L) and 47.5% of isolates showing intermediate susceptibility (MICpen = 0.12-1 mg/L). The most frequent resistance determinant (72.4% isolates) was the Asp345 insertion in penA, both as a single mutation and in combination with other mutations, particularly with the substitution Leu421Pro in ponA (39.0%). Mutations affecting the influx and efflux of drugs were also found, including amino acid substitutions in PorB (26.8% isolates) and delA in the promoter region of mtrR (22.8%). The accumulation of mutations in chromosomal genes (penA, pon, porA, and mtrR) led to a stepwise increase in MICpen to values characteristic of intermediate resistance. The presence of blaTEM plasmids was found in 25 isolates (4.8%), resulting in a strong increase in resistance to penicillin (MICpen > 16 mg/L) compared with the chromosomal mutations; 23 plasmids were of the African type with TEM-1 beta-lactamase, and two plasmids were of the Toronto/Rio type with TEM-135 beta-lactamase. Only three isolates were found with reduced susceptibility to ceftriaxone, with MICcef = 0.12-0.25 mg/L. Sequencing of penA did not reveal mutations associated with resistance to third-generation cephalosporins, and the gene structure was non-mosaic. The majority of isolates (21 of 25) carrying the blaTEM plasmid also contained the conjugative plasmid with tetM (resistance to tetracyclines), consistent with previously reported data that the presence of the conjugative plasmid facilitates the transfer of other plasmids associated with antimicrobial resistance.