{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T05:28:18Z","timestamp":1790659698460,"version":"4.1.0"},"reference-count":34,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2023,1,13]],"date-time":"2023-01-13T00:00:00Z","timestamp":1673568000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012190","name":"Ministry of Science and Higher Education of the Russian Federation","doi-asserted-by":"publisher","award":["075-15-2019-1660"],"award-info":[{"award-number":["075-15-2019-1660"]}],"id":[{"id":"10.13039\/501100012190","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012190","name":"Ministry of Science and Higher Education of the Russian Federation","doi-asserted-by":"publisher","award":["056-03-2021-124"],"award-info":[{"award-number":["056-03-2021-124"]}],"id":[{"id":"10.13039\/501100012190","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Ministry of Health of the Russian Federation","award":["075-15-2019-1660"],"award-info":[{"award-number":["075-15-2019-1660"]}]},{"name":"Ministry of Health of the Russian Federation","award":["056-03-2021-124"],"award-info":[{"award-number":["056-03-2021-124"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antibiotics"],"abstract":"<jats:p>The aim of this work was to study the resistance to macrolides (azithromycin) in the modern Russian population of N. gonorrhoeae with the analysis of genetic resistance determinants. Azithromycin is not used to treat gonococcal infection in Russia. However, among 162 isolates collected in 2020\u20132021, 22 isolates (13.6%) were phenotypically resistant to azithromycin. Mutations in 23S rRNA genes were found only in two isolates; erm and mefA genes were absent. Azithromycin resistance was shown to be predominantly associated with mutations in the mtrR and mtrD genes of the MtrCDE efflux pump and their mosaic alleles which may have formed due to a horizontal transfer from N. meningitidis. A total of 30 types of mtrR alleles and 10 types of mtrD alleles were identified including mosaic variants. Matching between the mtrR and mtrD alleles was revealed to indicate the cooperative molecular evolution of these genes. A link between the mtrR and mtrD alleles and NG-MAST types was found only for NG-MAST 228 and 807, typical of N. gonorrhoeae in Russia. The high level of resistance to azithromycin in Russia may be related to the spread of multiple transferable resistance to antimicrobials regardless of their use in the treatment of gonococcal infection.<\/jats:p>","DOI":"10.3390\/antibiotics12010170","type":"journal-article","created":{"date-parts":[[2023,1,16]],"date-time":"2023-01-16T02:29:55Z","timestamp":1673836195000},"page":"170","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Azithromycin Susceptibility Testing and Molecular Investigation of Neisseria gonorrhoeae Isolates Collected in Russia, 2020\u20132021"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9416-875X","authenticated-orcid":false,"given":"Ilya","family":"Kandinov","sequence":"first","affiliation":[{"name":"Center for Precision Genome Editing and Genetic Technologies for Biomedicine, Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow 119991, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0316-2262","authenticated-orcid":false,"given":"Boris","family":"Shaskolskiy","sequence":"additional","affiliation":[{"name":"Center for Precision Genome Editing and Genetic Technologies for Biomedicine, Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow 119991, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dmitry","family":"Kravtsov","sequence":"additional","affiliation":[{"name":"Center for Precision Genome Editing and Genetic Technologies for Biomedicine, Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow 119991, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra","family":"Vinokurova","sequence":"additional","affiliation":[{"name":"Center for Precision Genome Editing and Genetic Technologies for Biomedicine, Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow 119991, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0315-7428","authenticated-orcid":false,"given":"Sofya","family":"Gorshkova","sequence":"additional","affiliation":[{"name":"Center for Precision Genome Editing and Genetic Technologies for Biomedicine, Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow 119991, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexey","family":"Kubanov","sequence":"additional","affiliation":[{"name":"State Research Center of Dermatovenerology and Cosmetology, Russian Ministry of Health, Moscow 107076, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victoria","family":"Solomka","sequence":"additional","affiliation":[{"name":"State Research Center of Dermatovenerology and Cosmetology, Russian Ministry of Health, Moscow 107076, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia","family":"Shagabieva","sequence":"additional","affiliation":[{"name":"State Research Center of Dermatovenerology and Cosmetology, Russian Ministry of Health, Moscow 107076, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dmitry","family":"Deryabin","sequence":"additional","affiliation":[{"name":"State Research Center of Dermatovenerology and Cosmetology, Russian Ministry of Health, Moscow 107076, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ekaterina","family":"Dementieva","sequence":"additional","affiliation":[{"name":"Center for Precision Genome Editing and Genetic Technologies for Biomedicine, Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow 119991, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3183-318X","authenticated-orcid":false,"given":"Dmitry","family":"Gryadunov","sequence":"additional","affiliation":[{"name":"Center for Precision Genome Editing and Genetic Technologies for Biomedicine, Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow 119991, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,1,13]]},"reference":[{"key":"ref_1","unstructured":"(2021). Global progress report on HIV, viral hepatitis and sexually transmitted infections, 2021. The Global Health Sector Strategies 2016\u20132021: Actions for Impact, World Health Organization."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1080\/14737159.2022.2015329","article-title":"Antimicrobial resistance prediction in Neisseria gonorrhoeae: Current status and future prospects","volume":"22","author":"Golparian","year":"2022","journal-title":"Expert Rev. Mol. Diagn."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Shaskolskiy, B., Kandinov, I., Dementieva, E., and Gryadunov, D. (2022). Antibiotic resistance in Neisseria gonorrhoeae: Challenges in research and treatment. Microorganisms, 10.","DOI":"10.3390\/microorganisms10091699"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"S95","DOI":"10.1093\/cid\/ciac043","article-title":"Management of Neisseria gonorrhoeae in the United States: Summary of evidence from the development of the 2020 gonorrhea treatment recommendations and the 2021 Centers for Disease Control and Prevention sexually transmitted infection treatment guidelines","volume":"74","author":"Barbee","year":"2022","journal-title":"Clin. Infect. Dis."},{"key":"ref_5","unstructured":"(2016). WHO Guidelines for the Treatment of Neisseria gonorrhoeae, World Health Organization."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Unemo, M., Ross, J., Serwin, A.B., Gomberg, M., Cusini, M., and Jensen, J.S. (2020). 2020 European guideline for the diagnosis and treatment of gonorrhoea in adults. Int. J. STD AIDS, 956462420949126.","DOI":"10.1177\/0956462420949126"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1186\/s13756-020-00805-7","article-title":"Azithromycin resistant gonococci: A literature review","volume":"9","author":"Derbie","year":"2020","journal-title":"Antimicrob. Resist. Infect. Control"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"George, C.R.R., Enriquez, R.P., Gatus, B.J., Whiley, D.M., Lo, Y.R., Ishikawa, N., Wi, T., and Lahra, M.M. (2019). Systematic review and survey of Neisseria gonorrhoeae ceftriaxone and azithromycin susceptibility data in the Asia Pacific, 2011 to 2016. PLoS ONE, 14.","DOI":"10.1371\/journal.pone.0213312"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"e85","DOI":"10.1097\/OLQ.0000000000001303","article-title":"Characterization of 2 Neisseria gonorrhoeae strains with high-level azithromycin resistance isolated in 2015 and 2018 in Japan","volume":"48","author":"Shimuta","year":"2021","journal-title":"Sex Transm. Dis."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Mlynarczyk-Bonikowska, B., Kowalewski, C., Krolak-Ulinska, A., and Marusza, W. (2022). Molecular mechanisms of drug resistance and epidemiology of multidrug-resistant variants of Neisseria gonorrhoeae. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms231810499"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"3812","DOI":"10.1128\/AAC.00309-10","article-title":"High-level azithromycin resistance occurs in Neisseria gonorrhoeae as a result of a single point mutation in the 23S rRNA genes","volume":"54","author":"Chisholm","year":"2010","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1242","DOI":"10.1093\/jac\/dky017","article-title":"Azithromycin-resistant Neisseria gonorrhoeae spreading amongst men who have sex with men (MSM) and heterosexuals in New South Wales, Australia, 2017","volume":"73","author":"Whiley","year":"2018","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Zhou, Q., Liu, J., Chen, S., Xu, W., Han, Y., and Yin, Y. (2021). The accuracy of molecular detection targeting the mutation C2611T for detecting moderate-level azithromycin resistance in Neisseria gonorrhoeae: A systematic review and meta-analysis. Antibiotics, 10.","DOI":"10.3390\/antibiotics10091027"},{"key":"ref_14","unstructured":"The European Committee on Antimicrobial Susceptibility Testing (2022, September 01). Breakpoint Tables for Interpretation of MICs and Zone Diameters. Version 12.0. Available online: https:\/\/www.eucast.org\/clinical_breakpoints."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"4155","DOI":"10.1093\/nar\/gkab213","article-title":"Structures of Neisseria gonorrhoeae MtrR-operator complexes reveal molecular mechanisms of DNA recognition and antibiotic resistance-conferring clinical mutations","volume":"49","author":"Beggs","year":"2021","journal-title":"Nucl. Acids Res."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"evab287","DOI":"10.1093\/gbe\/evab287","article-title":"Global emergence and dissemination of Neisseria gonorrhoeae ST-9363 isolates with reduced susceptibility to azithromycin","volume":"14","author":"Joseph","year":"2022","journal-title":"Genome Biol. Evol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"e02281-18","DOI":"10.1128\/mBio.02281-18","article-title":"Mechanistic basis for decreased antimicrobial susceptibility in a clinical isolate of Neisseria gonorrhoeae possessing a mosaic-like mtr efflux pump locus","volume":"9","author":"Reimche","year":"2018","journal-title":"mBio"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1304","DOI":"10.1128\/JCM.03195-15","article-title":"Genomic epidemiology and molecular resistance mechanisms of azithromycin-resistant Neisseria gonorrhoeae in Canada from 1997 to 2014","volume":"54","author":"Demczuk","year":"2016","journal-title":"J. Clin. Microbiol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1113","DOI":"10.1099\/jmm.0.074286-0","article-title":"A Neisseria gonorrhoeae strain with a meningococcal mtrR sequence","volume":"63","author":"Trembizki","year":"2014","journal-title":"J. Med. Microbiol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"3877","DOI":"10.1128\/AAC.47.12.3877-3880.2003","article-title":"Acquired macrolide resistance genes in pathogenic Neisseria spp. isolated between 1940 and 1987","volume":"47","author":"Cousin","year":"2003","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"2503","DOI":"10.1128\/AAC.44.9.2503-2506.2000","article-title":"Identification of the conjugative mef gene in clinical Acinetobacter junii and Neisseria gonorrhoeae isolates","volume":"44","author":"Luna","year":"2000","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"2471","DOI":"10.1093\/jac\/dkw182","article-title":"Molecular epidemiology and mechanisms of resistance of azithromycin-resistant Neisseria gonorrhoeae isolated in France during 2013-14","volume":"71","author":"Belkacem","year":"2016","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"e02024-18","DOI":"10.1128\/JCM.02024-18","article-title":"Summary and trends of the Russian Gonococcal Antimicrobial Surveillance Programme, 2005 to 2016","volume":"57","author":"Kubanov","year":"2019","journal-title":"J. Clin. Microbiol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.ijid.2020.01.020","article-title":"Genetic diversity of Neisseria gonorrhoeae multi-antigen sequence types in Russia and Europe","volume":"93","author":"Shaskolskiy","year":"2020","journal-title":"Int. J. Infect. Dis."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Aniskevich, A., Shimanskaya, I., Boiko, I., Golubovskaya, T., Golparian, D., Stanislavova, I., Jacobsson, S., Adaskevich, A., and Unemo, M. (2021). Antimicrobial resistance in Neisseria gonorrhoeae isolates and gonorrhoea treatment in the Republic of Belarus, Eastern Europe, 2009-2019. BMC Infect. Dis., 21.","DOI":"10.1186\/s12879-021-06184-7"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Karymbaeva, S., Boiko, I., Jacobsson, S., Mamaeva, G., Ibraeva, A., Usupova, D., Golparian, D., and Unemo, M. (2021). Antimicrobial resistance and molecular epidemiological typing of Neisseria gonorrhoeae isolates from Kyrgyzstan in Central Asia, 2012 and 2017. BMC Infect. Dis., 21.","DOI":"10.1186\/s12879-021-06262-w"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Kandinov, I., Dementieva, E., Kravtsov, D., Chestkov, A., Kubanov, A., Solomka, V., Deryabin, D., Gryadunov, D., and Shaskolskiy, B. (2020). Molecular typing of Neisseria gonorrhoeae clinical isolates in Russia, 2018-2019: A link between penA alleles and NG-MAST types. Pathogens, 9.","DOI":"10.3390\/pathogens9110941"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"e452","DOI":"10.1016\/S2666-5247(22)00044-1","article-title":"Europe-wide expansion and eradication of multidrug-resistant Neisseria gonorrhoeae lineages: A genomic surveillance study","volume":"3","author":"Cole","year":"2022","journal-title":"Lancet Microbe"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/j.jgar.2018.11.011","article-title":"Antimicrobial resistance and molecular characterisation of Neisseria gonorrhoeae isolates in Fukuoka, Japan, 1996-2016","volume":"17","author":"Tanaka","year":"2019","journal-title":"J. Glob. Antimicrob. Resist."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Shaskolskiy, B., Dementieva, E., Kandinov, I., Filippova, M., Petrova, N., Plakhova, X., Chestkov, A., Kubanov, A., Deryabin, D., and Gryadunov, D. (2019). Resistance of Neisseria gonorrhoeae isolates to beta-lactams (benzylpenicillin and ceftriaxone) in Russia, 2015-2017. PLoS ONE, 14.","DOI":"10.1371\/journal.pone.0220339"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"2651","DOI":"10.1128\/AAC.45.9.2651-2654.2001","article-title":"Multidrug-resistant strains of Neisseria gonorrhoeae in Greece","volume":"45","author":"Mavroidi","year":"2001","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1166","DOI":"10.1093\/bioinformatics\/bts091","article-title":"Unipro UGENE: A unified bioinformatics toolkit","volume":"28","author":"Okonechnikov","year":"2012","journal-title":"Bioinformatics"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1071\/SH18225","article-title":"Genotypic determinants of fluoroquinolone and macrolide resistance in Neisseria gonorrhoeae","volume":"16","author":"Hall","year":"2019","journal-title":"Sex Health"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1497","DOI":"10.1086\/383047","article-title":"Rapid sequence-based identification of gonococcal transmission clusters in a large metropolitan area","volume":"189","author":"Martin","year":"2004","journal-title":"J. Infect. Dis."}],"container-title":["Antibiotics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2079-6382\/12\/1\/170\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T18:05:39Z","timestamp":1760119539000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2079-6382\/12\/1\/170"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,1,13]]},"references-count":34,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2023,1]]}},"alternative-id":["antibiotics12010170"],"URL":"https:\/\/doi.org\/10.3390\/antibiotics12010170","relation":{},"ISSN":["2079-6382"],"issn-type":[{"value":"2079-6382","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,1,13]]}}}