Microarray technologies for analysis of genetic determinants of Neisseria gonorrhoeae antimicrobial resistance
- Authors: Shaskolskiy B.L.1, Kravtsov D.V.1, Kandinov I.D.1, Gryadunov D.A.1, Shpilevaya M.V.2, Shagabieva J.Z.2, Nosov N.Y.2
-
Affiliations:
- Center for Precision Genome Editing and Genetic Technologies for Biomedicine, Engelhardt Institute of Molecular Biology, Russian Academy of Sciences
- State Research Center of Dermatovenereology and Cosmetology
- Issue: Vol 101, No 1 (2025)
- Pages: 85-97
- Section: ORIGINAL STUDIES
- URL: https://journals.rcsi.science/0042-4609/article/view/287234
- DOI: https://doi.org/10.25208/vdv16837
- ID: 287234
Cite item
Full Text
Abstract
Background. Neisseria gonorrhoeae exhibits a remarkable capacity for rapid antimicrobial resistance development. Globally, the prevalence of antimicrobial-resistant N. gonorrhoeae isolates continues to rise steadily, raising concerns about the potential emergence of untreatable infections.
Aims. This work updates the distribution patterns of genetic resistance determinants in contemporary Russian clinical N. gonorrhoeae isolates to key antimicrobial agents, utilizing hydrogel microarray technology.
Methods. The study included 360 N. gonorrhoeae isolates collected at the Federal State Research Center of Dermatovenereology and Cosmetology between 2019 and 2023. The susceptibility of N. gonorrhoeae to penicillin, ceftriaxone, tetracycline, azithromycin, and ciprofloxacin was determined through serial dilution in agar, with the minimum inhibitory concentration (MIC) subsequently calculated. Genetic determinants of antimicrobial resistance in N. gonorrhoeae were identified using hydrogel microarray technology.
Results. The current data on the distribution of genetic determinants associated with antimicrobial resistance in N. gonorrhoeae are presented in this study. In the Russian population of gonococcus dynamic shifts are underway, leading to a redistribution of the proportion of isolates resistant or susceptible to various antimicrobial agents. Since 2020, a marked increase has been observed in the proportion of N. gonorrhoeae isolates resistant to azithromycin and ciprofloxacin. Concurrently, susceptibility to penicillin has rebounded, while the entire gonococcal population remains fully susceptible to ceftriaxone. The validated microarray-based NG-TEST diagnostic kit enables rapid detection of ceftriaxone resistance in N. gonorrhoeae by simultaneously identifying resistance-associated genetic markers in the penA, ponA, and porB genes, combined with MIC calculation.
Conclusion. Microarray technologies for detecting antimicrobial resistance genetic determinants in N. gonorrhoeae serve as a complementary tool for identifying resistant strains. Microarray-based analysis informs tailored treatment strategies for patients and enables population-level surveillance of antimicrobial resistance trends in N. gonorrhoeae.
Full Text
##article.viewOnOriginalSite##About the authors
Boris L. Shaskolskiy
Center for Precision Genome Editing and Genetic Technologies for Biomedicine, Engelhardt Institute of Molecular Biology, Russian Academy of Sciences
Author for correspondence.
Email: bls@shaskolskiy.ru
ORCID iD: 0000-0002-0316-2262
Cand. Sci. (Chem.)
Russian Federation, 32 Vavilova street, 119991 MoscowDmitry V. Kravtsov
Center for Precision Genome Editing and Genetic Technologies for Biomedicine, Engelhardt Institute of Molecular Biology, Russian Academy of Sciences
Email: solo13.37@yandex.ru
ORCID iD: 0000-0003-4180-6898
SPIN-code: 5381-7087
Russian Federation, 32 Vavilova street, 119991 Moscow
Ilya D. Kandinov
Center for Precision Genome Editing and Genetic Technologies for Biomedicine, Engelhardt Institute of Molecular Biology, Russian Academy of Sciences
Email: ilya9622@gmail.com
ORCID iD: 0000-0001-9416-875X
SPIN-code: 8118-6614
32 Vavilova street, 119991 Moscow
Dmitry A. Gryadunov
Center for Precision Genome Editing and Genetic Technologies for Biomedicine, Engelhardt Institute of Molecular Biology, Russian Academy of Sciences
Email: grad@biochip.ru
ORCID iD: 0000-0003-3183-318X
SPIN-code: 6341-2455
Dr. Sci. (Biol.)
Russian Federation, 32 Vavilova street, 119991 MoscowMarina V. Shpilevaya
State Research Center of Dermatovenereology and Cosmetology
Email: aniram1970@list.ru
ORCID iD: 0000-0002-9957-4009
SPIN-code: 6600-3311
Cand. Sci. (Biol.)
Russian Federation, 3/6, Korolenko street,107076 MoscowJulia Z. Shagabieva
State Research Center of Dermatovenereology and Cosmetology
Email: shagabieva1412@mail.ru
ORCID iD: 0000-0002-7595-0276
SPIN-code: 7270-5113
Cand. Sci. (Chem.)
Russian Federation, 3/6, Korolenko street,107076 MoscowNikita Y. Nosov
State Research Center of Dermatovenereology and Cosmetology
Email: nosovnj@mail.ru
ORCID iD: 0000-0002-3967-8359
SPIN-code: 8806-8539
Cand. Sci. (Biol.)
Russian Federation, 3/6, Korolenko street,107076 MoscowReferences
- Global health sector strategies on, respectively, HIV, viral hepatitis and sexually transmitted infections for the period 2022–2030. Geneva, Switzerland: World Health Organization; 2022. URL: https://www.who.int/publications/i/item/9789240053779
- Shaskolskiy B, Kandinov I, Demetieva E, Gryadunov D. Antibiotic Resistance in Neisseria gonorrhoeae: Challenges in Research and Treatment. Microorganisms. 2022;10(9):1699. doi: 10.3390/microorganisms10091699
- Maubaret C, Caméléna F, Mrimèche M, Braille A, Liberge M, Mainardis M, et al. Two cases of extensively drug-resistant (XDR) Neisseria gonorrhoeae infection combining ceftriaxone-resistance and high-level azithromycin resistance, France, November 2022 and May 2023. Euro Surveill. 2023;28(37):2300456. doi: 10.2807/1560-7917.ES.2023.28.37.2300456
- Pleininger S, Indra A, Golparian D, Heger F, Schindler S, Jacobsson S, et al. Extensively drug-resistant (XDR) Neisseria gonorrhoeae causing possible gonorrhoea treatment failure with ceftriaxone plus azithromycin in Austria, April 2022. Euro Surveill. 2022;27(24):2200455. doi: 10.2807/1560-7917.ES.2022.27.24.2200455
- Красносельских Т.В., Соколовский Е.В., Рахматулина М.Р., Новоселова Е.Ю., Мелехина Л.Е. Заболеваемость сифилисом и некоторыми другими ИППП в Российской Федерации: прошлое, настоящее и пути достижения контроля эпидемиологической ситуации в будущем. Вестник дерматологии и венерологии. 2023;99(4):41–59. [Krasnoselskikh TV, Sokolovskiy EV, Rakhmatulina MR, Novoselova EYu, Melekhina LE. Syphilis and some other STIs in the Russian Federation: past, present and ways to control of the epidemiological situation in the future. Vestnik Dermatologii i Venerologii. 2023;99(4):41–59. (In Russ.)] doi: 10.25208/vdv13726
- Шагабиева Ю.З., Носов Н.Ю., Шпилевая М.В., Дерябин Д.Г., Образцова О.А., Никонорова Е.Р., и др. Анализ динамики устойчивости Neisseria gonorrhоeaе к антимикробным препаратам в РФ за период 2005–2021 гг. Вестник дерматологии и венерологии. 2023;99(3):53–62. [Shagabieva JZ, Nosov NYu, Shpilevaya MV, Deryabin DG, Obraztsova OA, Nikonorova ER, et al. Analysis of the dynamics of Neisseria gonorrhоeaе resistance to antimicrobial drugs in the Russian Federation for the period 2005–2021. Vestnik Dermatologii i Venerologii. 2023;99(3):53–62. (In Russ.)] doi: 10.25208/vdv1410
- Xiaoyu Z, Yue Xi, Xiangdong G, Shaochun C. Ceftriaxone-Resistant Gonorrhea — China,2022. MMWR Morb Mortal Wkly Rep. 2024;73(12):255–259. doi: 10.15585/mmwr.mm7312a2
- Reimche JL, Pham CD, Joseph SJ, Hutton S, Cartee JC, Ruan Y, et al. Novel strain of multidrug non-susceptible Neisseria gonorrhoeae in the USA. Lancet Infect Dis. 2024;24(3):e149–e151. doi: 10.1016/S1473-3099(23)00785-5
- Day M, Pitt R, Mody N, Saunders J, Rai R, Nori A, et al. Detection of 10 cases of ceftriaxone-resistant Neisseria gonorrhoeae in the United Kingdom, December 2021 to June 2022. Euro Surveill. 2022;27(46):2200803. doi: 10.2807/1560-7917.ES.2022.27.46.2200803
- Crucitti T, Belinga S, Fonkoua M, Abanda M, Mbanzouen W, Sokeng E, et al. Sharp increase in ciprofloxacin resistance of Neisseria gonorrhoeae in Yaounde, Cameroon: analyses of a laboratory database period 2012–2018. Int J STD AIDS. 2020;31(6):579–586. doi: 10.1177/0956462419897227
- Caméléna F, Mérimèche M, Brousseau J, Mainardis M, Verger P, Le Risbé C, et al. Emergence of Extensively Drug-Resistant Neisseria gonorrhoeae France,2023. Emerg Infect Dis. 2024;30(9):1903–1906. doi: 10.3201/eid3009.240557
- Kandinov I, Dementieva E, Filippova M, Vinokurova A, Gorshkova S, Kubanov A, et al. Emergence of Azithromycin-Resistant Neisseria gonorrhoeae Isolates Belonging to the NG-MAST Genogroup 12302 in Russia. Microorganisms. 2023;11(5):1226. doi: 10.3390/microorganisms11051226
- Updated recommendations for the treatment of Neisseria gonorrhoeae, Chlamydia trachomatis, and Treponema pallidum (syphilis)and new recommendations on syphilis testing and partner services. World Health Organization; 2024. URL: https://www.who.int/publications/i/item/9789240090767
- Gryadunov DA, Shaskolskiy BL, Nasedkina TV, Rubina AY, Zasedatelev AS. The EIMB Hydrogel Microarray Technology: Thirty Years Later. Acta Naturae. 2018;10(4):4–18. doi: 10.32607/20758251-2018-10-4-4-18
- Shaskolskiy B, Kandinov I, Kravtsov D, Vinokurova A, Gorshkova S, Filippova M, et al. Hydrogel Droplet Microarray for Genotyping Antimicrobial Resistance Determinants in Neisseria gonorrhoeae Isolates. Polymers (Basel). 2021;13(22):3889. doi: 10.3390/polym13223889
- Shaskolskiy B, Kandinov I, Kravtsov D, Filippova M, Chestkov A, Solomka V, et al. Prediction of ceftriaxone MIC in Neisseria gonorrhoeae using DNA microarray technology and regression analysis. J Antimicrob Chemother. 2021;76(12):3151–3158. doi: 10.1093/jac/dkab308
- Стандартные операционные процедуры по забору клинического материала у пациентов с подозрением на гонококковую инфекцию СОП № ГОН 002/04. М.: ДЭКС-ПРЕСС; 2008. 20 с. [Standartnye operacionnye procedury po zaboru klinicheskogo materiala u pacientov s podozreniem na gonokokkovuju infekciju (SOP No. GON 002/04). Moscow: DEKS-PRESS; 2008. (In Russ.)]
- Кубанова А.А., Фриго Н.В., Кубанов А.А., и др. Стандартные операционные процедуры по транспортировке и доставке клинического материала и выделенных культур возбудителя гонореи СОП № ГОН 001/03. М.: ДЭКС-ПРЕСС; 2008. 17 с. [Kubanova AA, Frigo NV, Kubanov AA, et al. Standartnye operacionnye procedury po transportirovke i dostavke klinicheskogo materiala i vydelennyh kul’tur vozbuditelja gonorei (SOP No. GON 001/03). Moscow: DEKS-PRESS; 2008. (In Russ.)]
- Кубанова А.А., Кубанов А.А., Фриго Н.В., и др. Стандартные операционные процедуры по проведению видовой идентификации возбудителя гонореи СОП № ГОН 003/04, СОП № ГОН 004/04, СОП № 005/04. М.: ДЭКС-ПРЕСС; 2008. 29 с. [Kubanova AA, Kubanov AA, Frigo NV, et al. Standartnye operacionnye procedury po provedeniju vidovoj identifikacii vozbuditelja gonorei (SOP No. GON 003/04; SOP No. GON 004/04; SOP No. GON 005/04). Moscow: DEKS-PRESS; 2008. (In Russ.)]
- Кубанова А.А., Фриго Н.В., Кубанов А.А. и др. Стандартные операционные процедуры по методам определения чувствительности гонококкa к антибактериальным препаратам. М.: ДЭКС-ПРЕСС; 2008. 16 с. [Kubanova AA, Frigo NV, Kubanov AA, et al. Standartnye operacionnye procedury po metodam opredelenija chuvstvitel’nosti gonokokka k antibakterial’nym preparatam (SOP No. GON 006/03). Moscow: DEKS-PRESS; 2008. 16 s. (In Russ.)]
- Kandinov I, Shaskolskiy B, Kravtsov D, Vinokurova A, Gorshkova S, Kubanov A, et al. Azithromycin Susceptibility Testing and Molecular Investigation of Neisseria gonorrhoeae Isolates Collected in Russia,2020–2021. Antibiotics (Basel). 2023;12(1):170. doi: 10.3390/antibiotics12010170
- Kubanov A, Solomka V, Plakhova X, Chestkov A, Petrova N, Shaskolskiy B, et al. Summary and Trends of the Russian Gonococcal Antimicrobial Surveillance Programme,2005 to 2016. J Clin Microbiol. 2019;57(6):e02024-18. doi: 10.1128/JCM.02024-18
- Roberts MC, Knapp JS. Transfer of beta-lactamase plasmids from Neisseria gonorrhoeae to Neisseria meningitidis and commensal Neisseria species by the 25.2-megadalton conjugative plasmid. Antimicrob Agents Chemother. 1988;32(9):1430–1432. doi: 10.1128/AAC.32.9.1430
- Shaskolskiy B, Dementieva E, Kandinov I, Filippova M, Petrova N, Plakhova X, et al. Resistance of Neisseria gonorrhoeae isolates to beta-lactam antibiotics (benzylpenicillin and ceftriaxone) in Russia,2015–2017. PLoS One. 2019;14(7):e0220339. doi: 10.1371/journal.pone.0220339
- Sánchez-Busó L, Yeats CA, Taylor B, Goater RJ, Underwood A, Abudahab K, et al. A community-driven resource for genomic epidemiology and antimicrobial resistance prediction of Neisseria gonorrhoeae at Pathogenwatch. Genome Med. 2021;13(1):61. doi: 10.1186/s13073-021-00858-2
Supplementary files
