Molecular typing of T. pallidum clinical isolates and their resistance to macrolides in the Russian Federation during 2018–2019

Cover Page


Cite item

Full Text

Abstract

Based on arp, tprII and tp0548 genes variability molecular typing of Treponema pallidum is a worldwide method for syphilis epidemiology analysis, including the ability to monitor antimicrobial-resistant variants of the causative agents of the disease.
The aim of the study is to characterize the molecular subtypes of T. pallidum isolated from syphilis patients’ clinical material in 2018–2019, to assess the known antibiotic resistance determinants presence, and to compare the results with known Russian and foreign data.
Materials and methods. 64 T. pallidum clinical isolates obtained from 10 regions of the Russian Federation: Astrakhan, Irkutsk, Kaluga, Moscow, Novosibirsk and Omsk regions, the Stavropol Territory, the Republic of Sakha (Yakutia), Tuva and Chuvashia were studied. The arp gene variability was estimated by the number of internal tandem repeats from 60 base pairs analyzed by PCR. The variability of tprII genes was based on the restriction fragment length polymorphism. The nucleotide sequence of the tp0548 gene with a length of 84 base pairs (positions 131–215) variable region, as well as the genetic determinants of macrolide resistance in the 23S rRNA gene, were studied by capillary sequencing.
Results. 14 d/f molecular subtype of T. pallidum was absolutely prevalent in 9 of 10 examined subjects of the Russian Federation, taking 93.75 % of the total number of clinical isolates, and it was consistent with data on its stable dominance over 2011–2017. The most common in Western Europe molecular  subtype of T. pallidum 14 d/g was found in the Kaluga and Omsk regions, taking 4.69 % of the analyzed samples. The molecular subtype of T. pallidum 14 b/f, sporadically but stably occurring over the many years of monitoring, was represented by a single clinical isolate (1.56 %) from the Republic of Tuva. A2058G 23S rRNA mutation causing resistance to macrolides was detected both in all (3 of 3) representatives molecular subtype 14 d/g and in 2 of 60 clinical isolates molecular subtype 14 d/f (from Moscow and Omsk region). In fact, the resistance to macrolides was found in 7.81 % T. pallidum Russian clinical isolates found during 2018–2019, that exceeds the WHO threshold level allowing to recommend a drug for the STI treatment.
Conclusion. The contemporary molecular epidemiology of syphilis in the Russian Federation is characterized by the dominance of the molecular subtype T. pallidum 14 d/f, and significantly distinguishes the local population from those in the neighboring states of Europe and Asia. The continued spread of the determinants of resistance to macrolides makes us cautious about the use of this group of drugs for the treatment of syphilis and is an argument in favor of an appropriate review of current clinical recommendations.

About the authors

V. S. Solomka

State Research Center of Dermatovenereology and Cosmetology, Ministry of Health of the Russian Federation

Email: fake@neicon.ru

Dr. Sci. (Biol.), Deputy Director for Research

Korolenko str., 3, bldg 6, Moscow, 107076, Russian Federation


Россия

T. M. Komyagina

State Research Center of Dermatovenereology and Cosmetology, Ministry of Health of the Russian Federation

Email: fake@neicon.ru
Junior Researcher, Department of the Laboratory Diagnostics of STIs and Dermatoses

Korolenko str., 3, bldg 6, Moscow, 107076, Russian Federation

Россия

A. V. Chestkov

State Research Center of Dermatovenereology and Cosmetology, Ministry of Health of the Russian Federation

Author for correspondence.
Email: chestkov@cnikvi.ru
Cand. Sci. (Biol.), Senior Researcher, Department of the Laboratory Diagnostics of STIs and Dermatoses

Korolenko str., 3, bldg 6, Moscow, 107076, Russian Federation

Россия

A. P. Obukhov

Republican Skin and Venereologic Dispensary of Republic of Tuva

Email: fake@neicon.ru

Cand. Sci. (Med.), Deputy Chief Physician

Schetinkina-Kravchenko str., 66, Kyzyl, 667000, Russian Federation


Россия

D. G. Deryabin

State Research Center of Dermatovenereology and Cosmetology, Ministry of Health of the Russian Federation

Email: fake@neicon.ru

Dr. Sci. (Biol.), Prof., Leading Researcher, Department of the Laboratory Diagnostics of STIs and Dermatoses

Korolenko str., 3, bldg 6, Moscow, 107076, Russian Federation



Россия

References

  1. Foxman B., Riley L. Molecular epidemiology: focus on infection. Am J Epidemiol. 2001;153(12):1135–1141.
  2. Сидоренко С. В., Соломка В.С., Кожушная О. С., Фриго Н. В. Методы типирования возбудителей инфекций, передаваемых половым путем. Вестник дерматологии и венерологии. 2010;3:12–21.
  3. Harper K. N., Liu H., Ocampo P. S., Steiner B. M., Martin A., Levert K. et al. The sequence of the acidic repeat protein (arp) gene differentiates venereal from nonvenereal Treponema pallidum subspecies, and the gene has evolved under strong positive selection in the subspecies that causes syphilis. FEMS Immunol Med Microbiol. 2008;53(3):322–332.
  4. Pillay A., Liu H., Chen C.Y., Holloway B., Sturm A.W., Steiner B. et al. Molecular subtyping of Treponema pallidum subspecies pallidum. Sex Transm Dis. 1998;25(8):408–414.
  5. Marra C. M., Sahi S. K., Tantalo L. C., Godornes C., Reid T., Behets F. et al. Enhanced molecular typing of Treponema pallidum: geographical distribution of strain types and association with neurosyphilis. J Infect Dis. 2010;202:1380–1388.
  6. Ma D. Y., Giacani L., Centurión-Lara A. The molecular epidemiology of Treponema pallidum subspecies pallidum. Sex Health. 2015;12(2):141–147.
  7. Stamm L.V. Global challenge of antibiotic-resistant Treponema pallidum. Antimicrob Agents Chemother. 2010;54(2):583–589.
  8. Кубанова А. А., Кубанов А. А., Фриго Н. В., Волков И. А., Ротанов С. В., Суворова А. А. Первый опыт молекулярного типирования и определения антибиотикорезистентности штаммов возбудителя сифилиса Treponema pallidum в Российской Федерации. Вестник дерматологии и венерологии. 2013;3:34–36.
  9. Кубанов А. А., Воробьев Д. В., Обухов А. П., Образцова О. А., Дерябин Д. Г. Молекулярная эпидемиология Treponema pallidum в приграничном регионе Российской Федерации (Республика Тыва). Молекулярная генетика, микробиология и вирусология. 2017;35(1):26–30.
  10. Khairullin R., Vorobyev D., Obukhov A., Kuular U.H., Kubanova A., Kubanov A. et al. Syphilis epidemiology in 1994–2013, molecular epidemiological strain typing and determination of macrolide resistance in Treponema pallidum in 2013–2014 in Tuva Republic, Russia. APMIS. 2016;124(7):595–602.
  11. Образцова О. А., Алейникова К. А., Обухов А. П., Кубанов А. А., Дерябин Д. Г. Генетические детерминанты резистентности к антимикробным препаратам и их представительство у различных молекулярных субтипов Treponema pallidum subsp. pallidum. Клиническая микробиология и антимикробная химиотерапия. 2018;20(3):216–221.
  12. Liu H., Rodes B., Chen C. Y., Steiner B. New tests for syphilis: rational design of a PCR method for detection of Treponema pallidum in clinical specimens using unique regions of the DNA polymerase I gene. J Clin Microbiol. 2001;39(5):1941–1946.
  13. Gallo Vaulet L., Grillová L., Mikalová L., Casco R., Rodríguez Fermepin M., Pando M. A. et al. Molecular typing of Treponema pallidum isolates from Buenos Aires, Argentina: Frequent Nichols-like isolates and low levels of macrolide resistance. PLoS One. 2017;12(2):e0172905.
  14. Lu Y., Wu Q., Wang L., Ji L. Molecular epidemiological survey of Treponema pallidum in pregnant women in the Zhabei District of Shanghai. J Med Microbiol. 2017;66(4):391–396.
  15. Grange P. A., Allix-Beguec C., Chanal J., Benhaddou N., Gerhardt P., Morini J. P. et al. Molecular subtyping of Treponema pallidum in Paris, France. Sex Transm Dis. 2013;40(8):641–644.
  16. Salado-Rasmussen K., Cowan S., Gerstoft J., Larsen H. K., Hoffmann S., Knudsen T. B. et al. Molecular Typing of Treponema pallidum in Denmark: A Nationwide Study of Syphilis. Acta Derm Venereol. 2016;96(2):202–206.
  17. Tipple C., McClure M. O., Taylor G. P. High prevalence of macrolide resistant Treponema pallidum strains in a London centre. Sex Transm Infect. 2011;87(6):486–488.
  18. Образцова О. А., Алейникова К. А., Кубанов А. А., Дерябин Д. Г. Вариабельность нуклеотидных последовательностей гена arp у российских изолятов Treponema pallidum. Журнал микробиологии, эпидемиологии и иммунобиологии (ЖМЭИ). 2018;1(3):45–52.
  19. Grillová L., Oppelt J., Mikalová L., Nováková M et al. Directly Sequenced Genomes of Contemporary Strains of Syphilis Reveal Recombination-Driven Diversity in Genes Encoding Predicted Surface-Exposed Antigens. Front Microbiol. 2019;10:1691.
  20. Wu B. R., Yang C. J., Tsai M. S., Lee K. Y., Lee N. Y., Huang W. C. et al. Multicentre surveillance of prevalence of the 23S rRNA A2058G and A2059G point mutations and molecular subtypes of Treponema pallidum in Taiwan, 2009–2013. Clin Microbiol Infect. 2014;20:802–807.
  21. Koizumi Y., Watabe T., Ota Y., Nakayama S. I., Asai N. et al. Cerebral Syphilitic Gumma Can Arise Within Months of Reinfection: A Case of Histologically Proven Treponema pallidum Strain Type 14 b/f Infection with Human Immunodeficiency Virus Positivity. Sex Transm Dis. 2018;45(2):e1–e4.
  22. Beale M. A., Marks M., Sahi S. K., Tantalo L. C., Nori A. V., French P. et al. Genomic epidemiology of syphilis reveals independent emergence of macrolide resistance across multiple circulating lineages. Nat Commun. 2019;10(1):3255.

Supplementary files

Supplementary Files
Action
1. JATS XML
Download

Copyright (c) 2019 Solomka V.S., Komyagina T.M., Chestkov A.V., Obukhov A.P., Deryabin D.G.

Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.
СМИ зарегистрировано Федеральной службой по надзору в сфере связи, информационных технологий и массовых коммуникаций (Роскомнадзор).
Регистрационный номер и дата принятия решения о регистрации СМИ: серия ПИ № ФС 77 - 60448 от 30.12.2014.


This website uses cookies

You consent to our cookies if you continue to use our website.

About Cookies