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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
Örebro University, School of Medical Sciences.
Örebro University, School of Medical Sciences.
Public Health England, London, UK.
European Centre for Disease Prevention and Control, Stockholm, Sweden.
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2016 (English)In: Journal of Antimicrobial Chemotherapy, ISSN 0305-7453, E-ISSN 1460-2091, Vol. 71, no 11, p. 3109-3116Article in journal (Refereed) Published
Abstract [en]

Objectives: 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.

Place, publisher, year, edition, pages
Oxford, United Kingdom: Oxford University Press, 2016. Vol. 71, no 11, p. 3109-3116
National Category
Microbiology Infectious Medicine
Research subject
Microbiology; Infectious Diseases
Identifiers
URN: urn:nbn:se:oru:diva-51527DOI: 10.1093/jac/dkw279ISI: 000388005100015PubMedID: 27432597Scopus ID: 2-s2.0-84994520359OAI: oai:DiVA.org:oru-51527DiVA, id: diva2:950999
Note

Funding Agencies:

Örebro County Council Research Committee

Foundation for Medical Research at Örebro University Hospital, Sweden

Available from: 2016-08-04 Created: 2016-08-02 Last updated: 2018-07-16Bibliographically approved

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Jacobsson, SusanneGolparian, DanielUnemo, Magnus

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