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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Veröffentlicht in:PloS one 2019-07, Vol.14 (7), p.e0220339-e0220339
Hauptverfasser: Shaskolskiy, Boris, Dementieva, Ekaterina, Kandinov, Ilya, Filippova, Marina, Petrova, Natalia, Plakhova, Xenia, Chestkov, Alexander, Kubanov, Alexey, Deryabin, Dmitry, Gryadunov, Dmitry
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creator Shaskolskiy, Boris
Dementieva, Ekaterina
Kandinov, Ilya
Filippova, Marina
Petrova, Natalia
Plakhova, Xenia
Chestkov, Alexander
Kubanov, Alexey
Deryabin, Dmitry
Gryadunov, Dmitry
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 (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.
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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 &gt; 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 &gt; 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. 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This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. 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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 &gt; 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 &gt; 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.</description><subject>Adult</subject><subject>Amides</subject><subject>Amino Acid Substitution - genetics</subject><subject>Amino acids</subject><subject>Anti-Bacterial Agents - pharmacology</subject><subject>Anti-Bacterial Agents - therapeutic use</subject><subject>Antibiotics</subject><subject>Antiinfectives and antibacterials</subject><subject>Antimicrobial agents</subject><subject>Antimicrobial resistance</subject><subject>Benzylpenicillin</subject><subject>Beta lactam antibiotics</subject><subject>Beta lactamases</subject><subject>beta-Lactam Resistance - drug effects</subject><subject>beta-Lactam Resistance - genetics</subject><subject>beta-Lactamases - genetics</subject><subject>Biology and Life Sciences</subject><subject>Ceftriaxone</subject><subject>Ceftriaxone - pharmacology</subject><subject>Ceftriaxone - therapeutic use</subject><subject>Cephalosporins</subject><subject>Clinical isolates</subject><subject>Cosmetology</subject><subject>Deoxyribonucleic acid</subject><subject>Dilution</subject><subject>Distribution</subject><subject>DNA</subject><subject>DNA chips</subject><subject>DNA microarrays</subject><subject>DNA Mutational Analysis</subject><subject>DNA sequencing</subject><subject>Dosage and administration</subject><subject>Drug resistance</subject><subject>Drug Resistance, Bacterial - drug effects</subject><subject>Drug Resistance, Bacterial - genetics</subject><subject>Drug therapy</subject><subject>Efflux</subject><subject>Female</subject><subject>Gene mutation</subject><subject>Gene sequencing</subject><subject>Genes</subject><subject>Gonorrhea</subject><subject>Gonorrhea - drug therapy</subject><subject>Gonorrhea - epidemiology</subject><subject>Gonorrhea - microbiology</subject><subject>Humans</subject><subject>Laboratories</subject><subject>Lactams</subject><subject>Male</subject><subject>Medicine and Health Sciences</subject><subject>Microbial drug resistance</subject><subject>Microbial Sensitivity Tests</subject><subject>Mitochondrial DNA</subject><subject>Molecular biology</subject><subject>Mutation</subject><subject>Neisseria gonorrhoeae - drug effects</subject><subject>Neisseria gonorrhoeae - genetics</subject><subject>Neisseria gonorrhoeae - isolation &amp; 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Dementieva, Ekaterina ; Kandinov, Ilya ; Filippova, Marina ; Petrova, Natalia ; Plakhova, Xenia ; Chestkov, Alexander ; Kubanov, Alexey ; Deryabin, Dmitry ; Gryadunov, Dmitry</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c659t-cff98ad175c4176cef26499599ae79997a85cd7579fc0054d20af4b9aada59613</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>Adult</topic><topic>Amides</topic><topic>Amino Acid Substitution - genetics</topic><topic>Amino acids</topic><topic>Anti-Bacterial Agents - pharmacology</topic><topic>Anti-Bacterial Agents - therapeutic use</topic><topic>Antibiotics</topic><topic>Antiinfectives and antibacterials</topic><topic>Antimicrobial agents</topic><topic>Antimicrobial resistance</topic><topic>Benzylpenicillin</topic><topic>Beta lactam antibiotics</topic><topic>Beta lactamases</topic><topic>beta-Lactam Resistance - drug effects</topic><topic>beta-Lactam Resistance - genetics</topic><topic>beta-Lactamases - genetics</topic><topic>Biology and Life Sciences</topic><topic>Ceftriaxone</topic><topic>Ceftriaxone - pharmacology</topic><topic>Ceftriaxone - therapeutic use</topic><topic>Cephalosporins</topic><topic>Clinical isolates</topic><topic>Cosmetology</topic><topic>Deoxyribonucleic acid</topic><topic>Dilution</topic><topic>Distribution</topic><topic>DNA</topic><topic>DNA chips</topic><topic>DNA microarrays</topic><topic>DNA Mutational Analysis</topic><topic>DNA sequencing</topic><topic>Dosage and administration</topic><topic>Drug resistance</topic><topic>Drug Resistance, Bacterial - drug effects</topic><topic>Drug Resistance, Bacterial - genetics</topic><topic>Drug therapy</topic><topic>Efflux</topic><topic>Female</topic><topic>Gene mutation</topic><topic>Gene sequencing</topic><topic>Genes</topic><topic>Gonorrhea</topic><topic>Gonorrhea - drug therapy</topic><topic>Gonorrhea - epidemiology</topic><topic>Gonorrhea - microbiology</topic><topic>Humans</topic><topic>Laboratories</topic><topic>Lactams</topic><topic>Male</topic><topic>Medicine and Health Sciences</topic><topic>Microbial drug resistance</topic><topic>Microbial Sensitivity Tests</topic><topic>Mitochondrial DNA</topic><topic>Molecular biology</topic><topic>Mutation</topic><topic>Neisseria gonorrhoeae - drug effects</topic><topic>Neisseria gonorrhoeae - genetics</topic><topic>Neisseria gonorrhoeae - isolation &amp; 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Medical Complete (Alumni)</collection><collection>https://resources.nclive.org/materials</collection><collection>Nursing &amp; Allied Health Database (Alumni Edition)</collection><collection>Meteorological &amp; Geoastrophysical Abstracts - Academic</collection><collection>ProQuest Engineering Collection</collection><collection>Biological Sciences</collection><collection>Agriculture Science Database</collection><collection>Health &amp; Medical Collection (Alumni Edition)</collection><collection>PML(ProQuest Medical Library)</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biological Science Database</collection><collection>Engineering Database</collection><collection>Nursing &amp; Allied Health Premium</collection><collection>Advanced Technologies &amp; Aerospace Database</collection><collection>ProQuest Advanced Technologies &amp; Aerospace Collection</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Environmental Science Database</collection><collection>Materials Science Collection</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>Engineering Collection</collection><collection>Environmental Science Collection</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Shaskolskiy, Boris</au><au>Dementieva, Ekaterina</au><au>Kandinov, Ilya</au><au>Filippova, Marina</au><au>Petrova, Natalia</au><au>Plakhova, Xenia</au><au>Chestkov, Alexander</au><au>Kubanov, Alexey</au><au>Deryabin, Dmitry</au><au>Gryadunov, Dmitry</au><au>Shafer, William M.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Resistance of Neisseria gonorrhoeae isolates to beta-lactam antibiotics (benzylpenicillin and ceftriaxone) in Russia, 2015-2017</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2019-07-25</date><risdate>2019</risdate><volume>14</volume><issue>7</issue><spage>e0220339</spage><epage>e0220339</epage><pages>e0220339-e0220339</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><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 (MICpen &gt; 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 &gt; 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.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>31344102</pmid><doi>10.1371/journal.pone.0220339</doi><orcidid>https://orcid.org/0000-0002-0316-2262</orcidid><oa>free_for_read</oa></addata></record>
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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
title Resistance of Neisseria gonorrhoeae isolates to beta-lactam antibiotics (benzylpenicillin and ceftriaxone) in Russia, 2015-2017
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