Туберкулез с лекарственной устойчивостью возбудителя: механизмы формирования и методы молекулярно-генетической диагностики

Обложка


Цитировать

Полный текст

Открытый доступ Открытый доступ
Доступ закрыт Доступ предоставлен
Доступ закрыт Доступ платный или только для подписчиков

Аннотация

Широкое распространение туберкулеза с лекарственной устойчивостью возбудителя — важная проблема общественного здравоохранения. Для лучшего понимания этого явления в статье суммируются современные представления о механизмах формирования устойчивости Mycobacterium tuberculosis к противотуберкулезным препаратам. Особое внимание уделяется механизму приобретенной резистентности, основанному на мутациях в генах, кодирующих мишени противотуберкулезных препаратов, или ферменты, переводящие пролекарство в активную форму, рассматривается влияние этих мутаций на возбудителя. В статье сделан акцент на ведущей роли молекулярно-генетических методов для диагностики лекарственной устойчивости M. tuberculosis и подчеркивается значимость этих методов для предотвращения расширения спектра резистентности возбудителя и профилактики распространения устойчивых клонов в популяции. Сравнение возможностей секвенирования и методов, основанных на ПЦР, позволило заключить, что на современном этапе развития технологий каждый из этих подходов целесообразно использовать для решения конкретных задач: отечественные тесты, основанные на ПЦР, — для ежедневной диагностики, а секвенирование — для фундаментальных исследований в области эволюции M. tuberculosis и эпидемиологического мониторинга. Предложены перспективные направления исследований резистентности M. tuberculosis, которые позволят выработать новые подходы для диагностики и лечения туберкулеза с лекарственной устойчивостью возбудителя и обеспечить эффективную персонализированную терапию.

Полный текст

Доступ закрыт

Об авторах

Атаджан Эргешович Эргешов

Центральный научно-исследовательский институт туберкулеза; Московский государственный медико-стоматологический университет имени А.И. Евдокимова

Автор, ответственный за переписку.
Email: ctri@ctri.ru
ORCID iD: 0000-0002-2494-9275

д.м.н., профессор, член-корреспондент РАН 

Россия, Москва; Москва

Софья Николаевна Андреевская

Центральный научно-исследовательский институт туберкулеза

Email: andsofia@mail.ru
ORCID iD: 0000-0002-4589-6133

к.м.н., старший научный сотрудник 

Россия, Москва

Татьяна Геннадьевна Смирнова

Центральный научно-исследовательский институт туберкулеза

Email: s_tatka@mail.ru
ORCID iD: 0000-0003-2886-1745

к.м.н. 

Россия, Москва

Лариса Николаевна Черноусова

Центральный научно-исследовательский институт туберкулеза

Email: lchernousova@mail.ru
ORCID iD: 0000-0001-6288-7549

д.б.н., профессор 

Россия, Москва

Список литературы

  1. Global antimicrobial resistance and use surveillance system (GLASS) report 2022. Geneva: World Health Organization; 2022.
  2. Ten threats to global health in 2019. Geneva: World Health Organization; 2019. Available from: https: //www.who.int/news-room/spotlight/ten-threats-to-globalhealth-in-2019
  3. Global tuberculosis report 2022. Geneva: World Health Organization; 2022.
  4. Туберкулез у взрослых: клинические рекомендации. — М., 2022. — 151 с. [Tuberculosis in adults: clinical recommendations. Moscow; 2022. 151 p. (In Russ.)]
  5. Meeting report of the WHO expert consultation on the definition of extensively drug-resistant tuberculosis, 27–29 October 2020. Geneva: World Health Organization; 2021.
  6. Васильева И.А., Тестов В.В., Стерликов С.А. Эпидемическая ситуация по туберкулезу в годы пандемии COVID-19 — 2020–2021 гг. // Туберкулез и болезни легких. — 2022. — Т. 100. — № 3. — С. 6–12. [Vasilyeva IА, Testov VV, Sterlikov SА. Tuberculosis situation in the years of the COVID-19 pandemic — 2020–2021. Tuberculosis and Lung Diseases. 2022;100(3):6–12. (In Russ.)] doi: http://doi.org/10.21292/2075-1230-2022-100-3-6-12
  7. Guidance for the surveillance of drug resistance in tuberculosis. 6th ed. Geneva: World Health Organization; 2020.
  8. Nguyen L. Antibiotic resistance mechanisms in M. tuberculosis: an update. Arch Toxicol. 2016;90(7):1585–5604. doi: https://doi.org/10.1007/s00204-016-1727-6
  9. Luthra S, Rominski A, Sander P. The Role of Antibiotic-Target-Modifying and Antibiotic-Modifying Enzymes in Mycobacterium abscessus Drug Resistance. Front Microbiol. 2018;9:2179. doi: https://doi.org/10.3389/fmicb.2018.02179
  10. Cook GM, Berney M, Gebhard S, et al. Physiology of mycobacteria. Adv Microb Physiol. 2009;55:81–182, 318–9. doi: https://doi.org/10.1016/S0065-2911(09)05502-7
  11. WHO consolidated guidelines on tuberculosis. Module 4: treatment — drug-resistant tuberculosis treatment, 2022 update. Geneva: World Health Organization; 2022.
  12. Singh R, Dwivedi SP, Gaharwar US, et al. Recent updates on drug resistance in Mycobacterium tuberculosis. J Appl Microbiol. 2020;128(6):1547–1567. doi: https://doi.org/10.1111/jam.14478
  13. Mabhula A, Singh V. Drug-resistance in Mycobacterium tuberculosis: where we stand. Medchemcomm. 2019;10(8):1342–1360. doi: https://doi.org/10.1039/c9md00057g
  14. Hameed HMA, Islam MM, Chhotaray C, et al. Molecular Targets Related Drug Resistance Mechanisms in MDR-, XDR-, and TDR- Mycobacterium tuberculosis Strains. Front Cell Infect Microbiol. 2018;8:114. doi: https://doi.org/10.3389/fcimb.2018.00114
  15. Wang JY, Sun HY, Wang JT, et al. Nine- to Twelve-Month Anti-Tuberculosis Treatment Is Associated with a Lower Recurrence Rate than 6-9-Month Treatment in Human Immunodeficiency Virus-Infected Patients: A Retrospective Population-Based Cohort Study in Taiwan. PLoS One. 2015;10(12):e0144136. doi: https://doi.org/10.1371/journal.pone.0144136
  16. Liu J, Bruhn DF, Lee RB, et al. Structure-Activity Relationships of Spectinamide Antituberculosis Agents: A Dissection of Ribosomal Inhibition and Native Efflux Avoidance Contributions. ACS Infect Dis. 2017;3(1):72–88. doi: https://doi.org/10.1021/acsinfecdis.6b00158
  17. Nasiruddin M, Neyaz MK, Das S. Nanotechnology-Based Approach in Tuberculosis Treatment. Tuberc Res Treat. 2017;2017:4920209. doi: https://doi.org/10.1155/2017/4920209
  18. Nasiri MJ, Haeili M, Ghazi M, et al. New Insights in to the Intrinsic and Acquired Drug Resistance Mechanisms in Mycobacteria. Front Microbiol. 2017;8:681. doi: https://doi.org/10.3389/fmicb.2017.00681
  19. Liu J, Shi W, Zhang S, et al. Mutations in Efflux Pump Rv1258c (Tap) Cause Resistance to Pyrazinamide, Isoniazid, and Streptomycin in M. tuberculosis. Front Microbiol. 2019;10:216. doi: https://doi.org/10.3389/fmicb.2019.00216
  20. Reeves AZ, Campbell PJ, Sultana R, et al. Aminoglycoside cross-resistance in Mycobacterium tuberculosis due to mutations in the 5’ untranslated region of whiB7. Antimicrob Agents Chemother. 2013;57(4):1857–1865. doi: https://doi.org/10.1128/AAC.02191-12
  21. Laws M, Jin P, Rahman KM. Efflux pumps in Mycobacterium tuberculosis and their inhibition to tackle antimicrobial resistance. Trends Microbiol. 2022;30(1):57–68. doi: https://doi.org/10.1016/j.tim.2021.05.001
  22. Kapp E, Malan SF, Joubert J, et al. Small Molecule Efflux Pump Inhibitors in Mycobacterium tuberculosis: A Rational Drug Design Perspective. Mini Rev Med Chem. 2018;18(1):72–86. doi: https://doi.org/10.2174/1389557517666170510105506
  23. Smith T, Wolff KA, Nguyen L. Molecular biology of drug resistance in Mycobacterium tuberculosis. Curr Top Microbiol Immunol. 2013;374:53–80. doi: https://doi.org/10.1007/82_2012_279
  24. Zaunbrecher MA, Sikes RD Jr, Metchock B, et al. Overexpression of the chromosomally encoded aminoglycoside acetyltransferase eis confers kanamycin resistance in Mycobacterium tuberculosis. Proc Natl Acad Sci U S A. 2009;106(47):20004–9. doi: https://doi.org/10.1073/pnas.0907925106
  25. Drlica K, Hiasa H, Kerns R, et al. Quinolones: action and resistance updated. Curr Top Med Chem. 2009;9(11):981–998. doi: https://doi.org/10.2174/156802609789630947
  26. Tao J, Han J, Wu H, et al. Mycobacterium fluoroquinolone resistance protein B, a novel small GTPase, is involved in the regulation of DNA gyrase and drug resistance. Nucleic Acids Res. 2013;41(4):2370–2381. doi: https://doi.org/10.1093/nar/gks1351
  27. Culyba MJ, Mo CY, Kohli RM. Targets for Combating the Evolution of Acquired Antibiotic Resistance. Biochemistry. 2015;54(23):3573–3582. doi: https://doi.org/10.1021/acs.biochem.5b00109
  28. Portelli S, Phelan JE, Ascher DB, et al. Understanding molecular consequences of putative drug resistant mutations in Mycobacterium tuberculosis. Sci Rep. 2018;8(1):15356. doi: https://doi.org/10.1038/s41598-018-33370-6
  29. Schön T, Miotto P, Köser CU, et al. Mycobacterium tuberculosis drug-resistance testing: challenges, recent developments and perspectives. Clin Microbiol Infect. 2017;23(3):154–160. doi: https://doi.org/10.1016/j.cmi.2016.10.022
  30. Koch A, Cox H, Mizrahi V. Drug-resistant tuberculosis: challenges and opportunities for diagnosis and treatment. Curr Opin Pharmacol. 2018;42:7–15. doi: https://doi.org/10.1016/j.coph.2018.05.013
  31. von Wintersdorff CJ, Penders J, van Niekerk JM, et al. Dissemination of Antimicrobial Resistance in Microbial Ecosystems through Horizontal Gene Transfer. Front Microbiol. 2016;7:173. doi: https://doi.org/10.3389/fmicb.2016.00173
  32. Dookie N, Rambaran S, Padayatchi N, et al. Evolution of drug resistance in Mycobacterium tuberculosis: a review on the molecular determinants of resistance and implications for personalized care. J Antimicrob Chemother. 2018;73(5):1138–1151. doi: https://doi.org/10.1093/jac/dkx506
  33. Borrell S, Gagneux S. Infectiousness, reproductive fitness and evolution of drug-resistant Mycobacterium tuberculosis. Int J Tuberc Lung Dis. 2009;13(12):1456–1466.
  34. Singla R. Drug-Resistant tuberculosis: Key strategies for a recalcitrant disease. Astrocyte 2017;4:53–62. doi: https://doi.org/10.4103/astrocyte.astrocyte_55_17
  35. Islam MM, Hameed HMA, Mugweru J, et al. Drug resistance mechanisms and novel drug targets for tuberculosis therapy. J Genet Genomics. 2017;44(1):21–37. doi: https://doi.org/10.1016/j.jgg.2016.10.002
  36. Cohen KA, Abeel T, Manson McGuire A, et al. Evolution of Extensively Drug-Resistant Tuberculosis over Four Decades: Whole Genome Sequencing and Dating Analysis of Mycobacterium tuberculosis Isolates from KwaZulu-Natal. PLoS Med. 2015;12(9):e1001880. doi: https://doi.org/10.1371/journal.pmed.1001880
  37. Manson AL, Cohen KA, Abeel T, et al. Evolution of Extensively Drug-Resistant Tuberculosis over Four Decades: Whole Genome Sequencing and Dating Analysis of Mycobacterium tuberculosis Isolates from KwaZulu-Natal. PLoS Med. 2015;12(9):e1001880. doi: https://doi.org/10.1371/journal.pmed.1001880
  38. Sun G, Luo T, Yang C, et al. Dynamic population changes in Mycobacterium tuberculosis during acquisition and fixation of drug resistance in patients. J Infect Dis. 2012;206(11):1724–1733. doi: https://doi.org/10.1093/infdis/jis601
  39. Mariam SH, Werngren J, Aronsson J, et al. Dynamics of antibiotic resistant Mycobacterium tuberculosis during long-term infection and antibiotic treatment. PLoS One. 2011;6(6):e21147. doi: https://doi.org/10.1371/journal.pone.0021147
  40. Zhang Y, Yew WW. Mechanisms of drug resistance in Mycobacterium tuberculosis: update 2015. Int J Tuberc Lung Dis. 2015;19(11):1276–1289. doi: https://doi.org/10.5588/ijtld.15.0389
  41. Эргешов А.Э., Черноусова Л.Н., Андреевская С.Н. Новые технологии диагностики лекарственно-устойчивого туберкулеза // Вестник Российской академии медицинских наук. — 2019. — Т. 74. — № 6. — C. 413–422. [Ergeshov AE, Chernousova LN, Andreevskaya SN. New technologies for the diagnosis of drug-resistant tuberculosis. Annals of the Russian Academy of Medical Sciences. 2019;74(6):413–422. (In Russ.)] doi: https://doi.org/10.15690/vramn1163
  42. Bertelli C, Greub G. Rapid bacterial genome sequencing: methods and applications in clinical microbiology. Clin Microbiol Infect. 2013;19(9):803–813. doi: https://doi.org/10.1111/1469-0691.12217
  43. Farhat MR, Shapiro BJ, Kieser KJ, et al. Genomic analysis identifies targets of convergent positive selection in drug-resistant Mycobacterium tuberculosis. Nat Genet. 2013;45(10):1183–1189. doi: https://doi.org/10.1038/ng.2747
  44. Merker M, Kohl TA, Roetzer A, et al. Whole genome sequencing reveals complex evolution patterns of multidrug-resistant Mycobacterium tuberculosis Beijing strains in patients. PLoS One. 2013;8(12):e82551. doi: https://doi.org/10.1371/journal.pone.0082551
  45. Zhang Q, Wan B, Zhou A, et al. Whole genome analysis of an MDR Beijing/W strain of Mycobacterium tuberculosis with large genomic deletions associated with resistance to isoniazid. Gene. 2016;582(2):128–136. doi: https://doi.org/10.1016/j.gene.2016.02.003
  46. Casali N, Nikolayevskyy V, Balabanova Y, et al. Evolution and transmission of drug-resistant tuberculosis in a Russian population. Nat Genet. 2014;46(3):279–286. doi: https://doi.org/10.1038/ng.2878
  47. Mohamed S, Köser CU, Salfinger M, et al. Targeted next-generation sequencing: a Swiss army knife for mycobacterial diagnostics? Eur Respir J. 2021;57(3):2004077. doi: https://doi.org/10.1183/13993003.04077-2020
  48. The use of next-generation sequencing technologies for the detection of mutations associated with drug resistance in Mycobacterium tuberculosis complex: technical guide. Geneva: World Health Organization; 2018 (WHO/CDS/TB/2018.19).
  49. Colman RE, Anderson J, Lemmer D, et al. Rapid Drug Susceptibility Testing of Drug-Resistant Mycobacterium tuberculosis Isolates Directly from Clinical Samples by Use of Amplicon Sequencing: a Proof-of-Concept Study. J Clin Microbiol. 2016;54(8):2058–2067. doi: https://doi.org/10.1128/JCM.00535-16
  50. Makhado NA, Matabane E, Faccin M, et al. Outbreak of multidrug-resistant tuberculosis in South Africa undetected by WHO-endorsed commercial tests: an observational study. Lancet Infect Dis. 2018;18(12):1350–1359. doi: https://doi.org/10.1016/S1473-3099(18)30496-1
  51. Feuerriegel S, Kohl TA, Utpatel C, et al. Rapid genomic first- and second-line drug resistance prediction from clinical Mycobacterium tuberculosis specimens using Deeplex-MycTB. Eur Respir J. 2021;57(1):2001796. doi: https://doi.org/10.1183/13993003.01796-2020
  52. Catalogue of mutations in Mycobacterium tuberculosis complex and their association with drug resistance. Geneva: World Health Organization; 2021.
  53. Андреевская С.Н. Динамика распространенности мутаций, ассоциированных с лекарственной устойчивостью, в современной популяции M. tuberculosis в Российской Федерации // Вестник Центрального научно-исследовательского института туберкулеза. — 2020. — S2. — С. 11–12. [Andreevskaya SN. Dynamics of the prevalence of mutations associated with drug resistance in the modern population of M. tuberculosis in the Russian Federation. Bulletin of the Central Scientific Research Institute of Tuberculosis. 2020;S2:11–12. (In Russ.)] doi: https://doi.org/10.7868/S2587667820060047
  54. Flandrois JP, Lina G, Dumitrescu O. MUBII-TB-DB: a database of mutations associated with antibiotic resistance in Mycobacterium tuberculosis. BMC Bioinformatics. 2014;15:107. doi: https://doi.org/10.1186/1471-2105-15-107
  55. Gagneux S, Long CD, Small PM, et al. The competitive cost of antibiotic resistance in Mycobacterium tuberculosis. Science. 2006;312(5782):1944–1946. doi: https://doi.org/10.1126/science.1124410
  56. Mariam DH, Mengistu Y, Hoffner SE, et al. Effect of rpoB mutations conferring rifampin resistance on fitness of Mycobacterium tuberculosis. Antimicrob Agents Chemother. 2004;48(4):1289–1294. doi: https://doi.org/10.1128/AAC.48.4.1289-1294.2004
  57. Koch A, Mizrahi V, Warner DF. The impact of drug resistance on Mycobacterium tuberculosis physiology: what can we learn from rifampicin? Emerg Microbes Infect. 2014;3(3):e17. doi: https://doi.org/10.1038/emi.2014.17
  58. Pym AS, Saint-Joanis B, Cole ST. Effect of katG mutations on the virulence of Mycobacterium tuberculosis and the implication for transmission in humans. Infect Immun. 2002;70(9):4955–4960. doi: https://doi.org/10.1128/IAI.70.9.4955-4960.2002
  59. Banerjee A, Dubnau E, Quemard A, et al. inhA, a gene encoding a target for isoniazid and ethionamide in Mycobacterium tuberculosis. Science. 1994;263(5144):227–230. doi: https://doi.org/10.1126/science.8284673
  60. Rouse DA, DeVito JA, Li Z, et al. Site-directed mutagenesis of the katG gene of Mycobacterium tuberculosis: effects on catalase-peroxidase activities and isoniazid resistance. Mol Microbiol. 1996;22(3):583–592. doi: https://doi.org/10.1046/j.1365-2958.1996.00133.x
  61. van Soolingen D, de Haas PE, van Doorn HR, et al. Mutations at amino acid position 315 of the katG gene are associated with high-level resistance to isoniazid, other drug resistance, and successful transmission of Mycobacterium tuberculosis in the Netherlands. J Infect Dis. 2000;182(6):1788–1790. doi: https://doi.org/10.1086/317598
  62. Sander P, Springer B, Prammananan T, et al. Fitness cost of chromosomal drug resistance-conferring mutations. Antimicrob Agents Chemother. 2002;46(5):1204–1211. doi: https://doi.org/10.1128/AAC.46.5.1204-1211.2002
  63. Comas I, Borrell S, Roetzer A, et al. Whole-genome sequencing of rifampicin-resistant Mycobacterium tuberculosis strains identifies compensatory mutations in RNA polymerase genes. Nat Genet. 2011;44(1):106–110. doi: https://doi.org/10.1038/ng.1038
  64. Al-Saeedi M, Al-Hajoj S. Diversity and evolution of drug resistance mechanisms in Mycobacterium tuberculosis. Infect Drug Resist. 2017;10:333–342. doi: https://doi.org/10.2147/IDR.S144446
  65. Gagneux S, Burgos MV, DeRiemer K, et al. Impact of bacterial genetics on the transmission of isoniazid-resistant Mycobacterium tuberculosis. PLoS Pathog. 2006;2(6):e61. doi: https://doi.org/10.1371/journal.ppat.0020061
  66. Fenner L, Egger M, Bodmer T, et al. Swiss HIV Cohort Study and the Swiss Molecular Epidemiology of Tuberculosis Study Group. Effect of mutation and genetic background on drug resistance in Mycobacterium tuberculosis. Antimicrob Agents Chemother. 2012;56(6):3047–3053. doi: https://doi.org/10.1128/AAC.06460-11
  67. Böttger EC, Springer B. Tuberculosis: drug resistance, fitness, and strategies for global control. Eur J Pediatr. 2008;167(2):141–148. doi: https://doi.org/10.1007/s00431-007-0606-9
  68. Practical manual on tuberculosis laboratory strengthening, 2022 update. Geneva: World Health Organization; 2022.

Дополнительные файлы

Доп. файлы
Действие
1. JATS XML
Скачать

© Издательство "Педиатръ", 2023



Данный сайт использует cookie-файлы

Продолжая использовать наш сайт, вы даете согласие на обработку файлов cookie, которые обеспечивают правильную работу сайта.

О куки-файлах