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

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...

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Autores principales: Shaskolskiy, Boris, Dementieva, Ekaterina, Kandinov, Ilya, Filippova, Marina, Petrova, Natalia, Plakhova, Xenia, Chestkov, Alexander, Kubanov, Alexey, Deryabin, Dmitry, Gryadunov, Dmitry
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6657886/
https://www.ncbi.nlm.nih.gov/pubmed/31344102
http://dx.doi.org/10.1371/journal.pone.0220339
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author Shaskolskiy, Boris
Dementieva, Ekaterina
Kandinov, Ilya
Filippova, Marina
Petrova, Natalia
Plakhova, Xenia
Chestkov, Alexander
Kubanov, Alexey
Deryabin, Dmitry
Gryadunov, Dmitry
author_facet Shaskolskiy, Boris
Dementieva, Ekaterina
Kandinov, Ilya
Filippova, Marina
Petrova, Natalia
Plakhova, Xenia
Chestkov, Alexander
Kubanov, Alexey
Deryabin, Dmitry
Gryadunov, Dmitry
author_sort Shaskolskiy, Boris
collection PubMed
description 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.
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spelling pubmed-66578862019-08-07 Resistance of Neisseria gonorrhoeae isolates to beta-lactam antibiotics (benzylpenicillin and ceftriaxone) in Russia, 2015–2017 Shaskolskiy, Boris Dementieva, Ekaterina Kandinov, Ilya Filippova, Marina Petrova, Natalia Plakhova, Xenia Chestkov, Alexander Kubanov, Alexey Deryabin, Dmitry Gryadunov, Dmitry PLoS One Research Article 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. Public Library of Science 2019-07-25 /pmc/articles/PMC6657886/ /pubmed/31344102 http://dx.doi.org/10.1371/journal.pone.0220339 Text en © 2019 Shaskolskiy et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Shaskolskiy, Boris
Dementieva, Ekaterina
Kandinov, Ilya
Filippova, Marina
Petrova, Natalia
Plakhova, Xenia
Chestkov, Alexander
Kubanov, Alexey
Deryabin, Dmitry
Gryadunov, Dmitry
Resistance of Neisseria gonorrhoeae isolates to beta-lactam antibiotics (benzylpenicillin and ceftriaxone) in Russia, 2015–2017
title Resistance of Neisseria gonorrhoeae isolates to beta-lactam antibiotics (benzylpenicillin and ceftriaxone) in Russia, 2015–2017
title_full Resistance of Neisseria gonorrhoeae isolates to beta-lactam antibiotics (benzylpenicillin and ceftriaxone) in Russia, 2015–2017
title_fullStr Resistance of Neisseria gonorrhoeae isolates to beta-lactam antibiotics (benzylpenicillin and ceftriaxone) in Russia, 2015–2017
title_full_unstemmed Resistance of Neisseria gonorrhoeae isolates to beta-lactam antibiotics (benzylpenicillin and ceftriaxone) in Russia, 2015–2017
title_short Resistance of Neisseria gonorrhoeae isolates to beta-lactam antibiotics (benzylpenicillin and ceftriaxone) in Russia, 2015–2017
title_sort resistance of neisseria gonorrhoeae isolates to beta-lactam antibiotics (benzylpenicillin and ceftriaxone) in russia, 2015–2017
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6657886/
https://www.ncbi.nlm.nih.gov/pubmed/31344102
http://dx.doi.org/10.1371/journal.pone.0220339
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