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WGS analysis and molecular resistance mechanisms of azithromycin-resistant (MIC >2 mg/L) Neisseria gonorrhoeae isolates in Europe from 2009 to 2014

dc.contributor.authorJacobsson, Susanne
dc.contributor.authorGolparian, Daniel
dc.contributor.authorCole, Michelle
dc.contributor.authorSpiteri, Gianfranco
dc.contributor.authorMartin, Irene
dc.contributor.authorBergheim, Thea
dc.contributor.authorBorrego, Maria José
dc.contributor.authorCrowley, Brendan
dc.contributor.authorCrucitti, Tania
dc.contributor.authorVan Dam, Alje P.
dc.contributor.authorHoffmann, Steen
dc.contributor.authorJeverica, Samo
dc.contributor.authorKohl, Peter
dc.contributor.authorMlynarczyk-Bonikowska, Beata
dc.contributor.authorPakarna, Gatis
dc.contributor.authorStary, Angelika
dc.contributor.authorStefanelli, Paola
dc.contributor.authorPavlik, Peter
dc.contributor.authorTzelepi, Eva
dc.contributor.authorAbad, Raquel
dc.contributor.authorHarris, Simon R.
dc.contributor.authorUnemo, Magnus
dc.date.accessioned2017-03-07T15:06:32Z
dc.date.available2017-03-07T15:06:32Z
dc.date.issued2016-11
dc.description.abstractOBJECTIVES: To elucidate the genome-based epidemiology and phylogenomics of azithromycin-resistant (MIC >2 mg/L) Neisseria gonorrhoeae strains collected in 2009-14 in Europe and clarify the azithromycin resistance mechanisms. METHODS: Seventy-five azithromycin-resistant (MIC 4 to >256 mg/L) N. gonorrhoeae isolates collected in 17 European countries during 2009-14 were examined using antimicrobial susceptibility testing and WGS. RESULTS: Thirty-six N. gonorrhoeae multi-antigen sequence typing STs and five phylogenomic clades, including 4-22 isolates from several countries per clade, were identified. The azithromycin target mutation A2059G (Escherichia coli numbering) was found in all four alleles of the 23S rRNA gene in all isolates with high-level azithromycin resistance (n = 4; MIC ≥256 mg/L). The C2611T mutation was identified in two to four alleles of the 23S rRNA gene in the remaining 71 isolates. Mutations in mtrR and its promoter were identified in 43 isolates, comprising isolates within the whole azithromycin MIC range. No mutations associated with azithromycin resistance were found in the rplD gene or the rplV gene and none of the macrolide resistance-associated genes [mef(A/E), ere(A), ere(B), erm(A), erm(B), erm(C) and erm(F)] were identified in any isolate. CONCLUSIONS: Clonal spread of relatively few N. gonorrhoeae strains accounts for the majority of the azithromycin resistance (MIC >2 mg/L) in Europe. The four isolates with high-level resistance to azithromycin (MIC ≥256 mg/L) were widely separated in the phylogenomic tree and did not belong to any of the main clades. The main azithromycin resistance mechanisms were the A2059G mutation (high-level resistance) and the C2611T mutation (low- and moderate-level resistance) in the 23S rRNA gene.pt_PT
dc.description.sponsorshipThe present work was supported by grants from theO¨ rebro County Council Research Committee and the Foundation for Medical Research at O¨ rebro University Hospital, Swedenpt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationJ Antimicrob Chemother. 2016 Nov;71(11):3109-3116. Epub 2016 Jul 17pt_PT
dc.identifier.doi10.1093/jac/dkw279pt_PT
dc.identifier.issn0305-7453
dc.identifier.urihttp://hdl.handle.net/10400.18/4543
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherOxford University Press/ British Society for Antimicrobial Chemotherapypt_PT
dc.relation.publisherversionhttps://academic.oup.com/jac/article-abstract/71/11/3109/2462045/WGS-analysis-and-molecular-resistance-mechanisms?redirectedFrom=fulltextpt_PT
dc.subjectAzithromycin-resistantpt_PT
dc.subjectNeisseria gonorrhoeaept_PT
dc.subjectEuropept_PT
dc.subjectAllelespt_PT
dc.subjectAzithromycinpt_PT
dc.subjectMutationpt_PT
dc.subjectAntimicrobial Susceptibility Testpt_PT
dc.subjectInfecções Sexualmente Transmissíveispt_PT
dc.titleWGS analysis and molecular resistance mechanisms of azithromycin-resistant (MIC >2 mg/L) Neisseria gonorrhoeae isolates in Europe from 2009 to 2014pt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.citation.endPage3116pt_PT
oaire.citation.issue11pt_PT
oaire.citation.startPage3109pt_PT
oaire.citation.titleJournal of Antimicrobial Chemotherapypt_PT
oaire.citation.volume71pt_PT
rcaap.rightsembargoedAccesspt_PT
rcaap.typearticlept_PT

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