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

Abstract

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 (MIC pen > 1 mg/L) and 47.5% of isolates showing intermediate susceptibility (MIC pen = 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 MIC pen to values characteristic of intermediate resistance. The presence of bla TEM plasmids was found in 25 isolates (4.8%), resulting in a strong increase in resistance to penicillin (MIC pen > 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 MIC cef = 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 bla TEM 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.

Plasmid mediated penicillin and tetracycline resistance among Neisseria gonorrhoeae isolates from Kenya

“…These findings indicate that resistance to penicillin in the analyzed Kenyan gonococci is also mediated by chromosomal modifications mechanisms in addition to the plasmid borne TEM. β-lactamase production in gonococci has been associated with resistant penicillin MICs [ 65 ] [ 66 ]. Contrary to these previous findings, this study identified two PPNG isolates which were not resistant to penicillin.…”

Molecular Typing of Neisseria gonorrhoeae Clinical Isolates in Russia, 2018–2019: A Link Between penA Alleles and NG-MAST Types

“…A total of 61 NG-MAST types were identified among the isolates collected in 2018–2019. Analysis of the Russian N. gonorrhoeae population considering NG-MAST types and genogroups carried out in our previous studies led to the conclusion about the predominantly local character of its formation and evolution, and phylogenetic analysis showed the difference between the most common Russian STs and the European STs [ 20 , 21 , 27 , 33 ]. This tendency was maintained for the Russian N. gonorrhoeae population in 2018–2019; NG-MAST 228, 807, 9486, and 1993 remained the most widespread types and retained their dominant position for many years.…”

“…Samples were collected by specialized medical organizations of dermatovenerological profiling, and each sample was collected from an individual patient. Sample collection, transportation, cultivation, phenotyping, and storage were performed according to a previously described protocol [ 20 , 21 ].…”

“…The Russian population of the causative agent of gonorrhea continues to demonstrate high resistance to penicillin, but no isolates resistant to ceftriaxone have been found to date [ 20 , 21 ]. This can be explained by the relative isolation of the Russian population of gonococci, as confirmed by the presence of sequence types (STs) and genogroups unique to the Russian Federation [ 22 ].…”

Immunoinformatics Prediction of an Epitope Based Peptide Vaccine for Neisseria Gonorrhea Dihydrolipoamide Acetyltransferase Protein

“…[5]Nucleic acid amplification tests (NAAT) are the preferred method used for diagnosis of N. Gonorrhea infection. [8] Furthermore, Neisseria Gonorrhea is able to accumulate different mutations leading to the emergence of clinical isolates with clinically significant levels of resistance to currently or previously used antibiotics such as sulfadrugs, penicillins and tetracyclines which has led the WHO to consider adding N. Gonorrhea infections to the category of untreatable infections [9][10][11][12]. With the absence of effective vaccines, and the lack of prolonged immunity after infection due to multiple evading mechanisms, society relies on antibiotics to reduce the spread of the gonococcus in the community [6,13,14].…”