Compensatory mutations as a mechanism for preserving virulence and viability of drug-resistant forms of Mycobacterium tuberculosis

Cover Page

Cite item

Full Text

Open Access Open Access
Restricted Access Access granted
Restricted Access Subscription or Fee Access

Abstract

Tuberculosis remains one of the leading causes of death from infectious diseases in the world. According to WHO data, tuberculosis is diagnosed annually in more than 100 million people and causes 4.5 thousand deaths. Despite a steady decline in the main epidemiological indicators for tuberculosis, the drug resistance of Mycobacterium tuberculosis (MBT) continues to increase steadily, and according to the Saint-Petersburg Research Institute for Phthisiopulmonology data that occures in all its localizations. There is a dangerous spread of multiple and broad drug resistance of MBT, and, most alarmingly, total resistance of MBT to all anti-tuberculosis drugs. The purpose of the review is to summarize current data on compensatory mutations that pose a serious threat, allowing to preserve the viability and virulence of drug-resistant forms of M. tuberculosis. Material and methods. The literature search was carried out using databases eLIBRARY.RU, MedLine, PubMed for 2000 - 2021. Results. MBT drug resistance, unlike other infections, results from accumulation of chromosomal mutations, rather than from plasmids and mobile genetic elements. Currently, mutations in genes associated with resistance to almost all anti-tuberculosis drugs are known. Drug resistance acquisition has pleiotropic effects, i.e. it is associated with known biological costs, often reducing the viability and virulence of MBT. But numerous studies have established that in the course of MBT evolution, so-called compensatory mutations are acquired in other genes, that can interact epistatically with resistance mutations, thereby reducing the «cost» of adaptiveness while maintaining the viability and virulence of the pathogen. Conclusion. The current crisis of classical antibacterial therapy necessitates further in-depth study of compensatory mutations, mainly to find «antimutators» as an alternative therapy to improve the effectiveness of tuberculosis treatment.

Full Text

Restricted Access

About the authors

Boris Izrailevich Vishnevsky

St. Petersburg State Research Institute of Phthisiopulmonology of the Ministry of Health of the Russian Federation

Author for correspondence.
Email: bivish@rambler.ru
Scientific Advisor; Doctor of Medical Sciences, Professor. Ligovsky pr. 2-4, St. Petersburg, 191036, Russian Federation

References

  1. World Tuberculosis Day. WHO Bulletin 24 March 2019. https://www.who.int>detai
  2. Яблонский П.К., Вишневский Б.И.,Соловьева Н.С., Маничева О.А. Догонадзе М.З., Мельникова Н.Н., Журавлев В.Ю. Лекарственная устойчивость Mycоbacterium tuberculosis при различных локализациях заболевания. Инфекция и ммунитет. 2016; 2:133-40
  3. Furin J., Brigden G., Lessem E. Global progress and challenges in implementing new medications for treating multidrug-resistant tuberculosis. Emerg. Infect. Dis. 2016; 22 (3): e151430. https://doi.org/10.3201/eid2203.151430.
  4. Meeting report of the WHO expert consultation on the definition of extensively drug-resistant tuberculosis, 27-29 October 2020 ISBN 978-92-4-001866-2 (electronic version) https://www.who.int
  5. Udwadia ZF. MDR, XDR, TDR tuberculosis: ominous rogression. Thorax. 2012; 67: 286-8.
  6. WHO. Global tuberculosis report 2018. Geneva: World Health Organization; 2018. Available at: https://apps.who.int/iris/handle/10665/274453
  7. Вишневский Б.И. Лекарственная устойчивость микобактерий туберкулеза. Медицинский альянс. 2017; 1: 29-35.
  8. Roca I., Akova M., Baquero F. The goal threat of antimicrobial resistance: science for intervention. New Microbes New Infect. 2015; 6: 22-9. https://doi.org/10.1016/j.nmni.2015.02.007.
  9. Smith T., Wolf K., Nguen U. Molecular biology of drug resistance in Mycobacterium tuberculosis. Curr Top Microbiol Immunol. 2013; 374: 53-80. https://doi.org/10.1007/82_2012_279
  10. Наумов А.Г, Павлунин А.В. Механизмы развития лекарственной устойчивости Mycobacterium tuberculosis: есть ли шанс победить? Пульмонология. 2021; 31 (1): 100-8. https://doi.org/10.18093/0869-0189-2021-31-1-100-108
  11. Hameed H.M., Islam M.M., Chnotaray C. Mоlecular targets related drug resistance mechanism in MDR-, XDR-, and TDR-Mycobacterium tuberculosis strains. Front. Cell. Infect. Microbiol. 2018; 8: 114. https://doi.org/10.3389/fci
  12. Wang F., Shao L., Fan X., Shen Y., Diao N., Jin J., Sun F., Wu J., Chen J., Weng X. Evolution and transmission patterns of extensively drug-resistant tuberculosis in China. Antimicrob. Agents Chemother. 2015: 59: 818-25.
  13. Casali N., Nikolaevskyy V., Balabanova Y., Harris S., Ignatyeva O., Corander J., Nejentsev SHorstmann D., Brown T., Drobnievski F. Evolution and transmission of drug-resistant tuberculosis in a Russian population. Nat. Genet. 2014; 46: 279-86. https://doi.org/10.1038/ng.2878
  14. Coll F., Phelan J., Hill-Cawthorne G.A., Nair M.B., Mallard K., Ali S., Abdallah A.M., Alghamdi S., Alsomali M., Ahmed, A.O. Genome-wide analysis of multi-and extensively drug-resistant Mycobacterium tuberculosis. Nat. Genet. 2018: 50: 307.
  15. Kohanski M.A., DePristo M.A., Collins J.J. Sublethal antibiotic treatment leads to multidrug resistance via radical-induced mutagenesis. Molecular cell. 2010; 37: 311-20
  16. Вишневский Б.И., Яблонский П.К. Персистенция Mycobacterium tuberculosis - основа латентного туберкулеза. Обзор. МедАльянс. 2020; 3: 14-20.
  17. Zhang Y. Drug Resistant and Persistent Tuberculosis: Mechanisms and Drug Development. In: T.J. Dougherty MJP, editor, Antibiotic Discovery and Development. Springer Science+Business Media. 2012; 719-46.
  18. Kempf I., Zeitouni S The cost of antibiotic resistance: analysis and consequences. Pathol Biol (Paris). 2012; 60 (2): 9-14. https://doi.org/10.1016/j.patbio.2009.10.013.Review.
  19. MacLean R.C., Vogwill T. Limits to compensatory adaptation and the persistence of antibiotic resistance in pathogenic bacteria. Evol. Med. Public Health. 2014; 2015: 4-12. https://doi.org/10.1093/emph/eou032
  20. Andersson D.I., Hughes D. Antibiotic resistance and its cost: is it possible to reverse resistance? Nature reviews. Microbiology 2010; 8: 260-71.
  21. Ameeruddin N.U., Luke Elizabeth H. Impact of isoniazid resistance on virulence of global and south Indian clinical isolates of Mycobacterium tuberculosis. Tuberculosis (Edinb). 2014; 94 (6): 557-63. https://doi.org/10.1016/j.tube.2014.08.011
  22. Gygli S.M., Borrell S., Trauner A., Gagneux S. FEMS Microbiol Rev. 2017; 1, 41 (3): 354-73. https://doi.org/10.1093/femsre/fux011.
  23. Muzondiwa D., Hlanze H., Reva O.N. The Epistatic Landscape of Antibiotic Resistance of Different Clades of Mycobacterium tuberculosis. Antibiotics. 2021; 10: 857. https://doi.org/10.3390/antibiotics10070857
  24. Ma P., Luo T., Ge L., Chen Z., Wang X., Zhao R., Liao W., Bao L.Compensatory effects of M. tuberculosis rpoB mutations outside the rifampicin resistance-determining region. Emerg Microbes Infect. 2021; 10 (1): 743-52. https://doi.org/10.1080/22221751.2021.1908096.
  25. Маничева О.А., Догонадзе М.З., Мельникова Н.Н., Вишневский Б.И., Маничев С.А. Фенотипическое свойство скорости роста Mycobacterium tuberculosis: зависимость от лекарственной чувствительности возбудителя, локализации туберкулеза, лечения. Инфекция и иммунитет. 2018; 8 (2): 175-86.
  26. Wang S., Zhou Y, Zhao B., Ou X., Xia H., Zheng Y., Song Y, Cheng Q., Wang X., Zhao Y. Characteristics of compensatory mutations in the rpoC gene and their association with compensated transmission of Mycobacterium tuberculosis. Front Med. 2020; 14 (1): 51-9. https://doi.org/10.1007/s11684-019-0720-x.
  27. Brandis G., Wrande M., Liljas L., Hughes D. Fitness-compensatory mutations in rifampicin-resistant RNA polymerase. Mol. Microbiol. 2012; 85 (1): 142-51. https://doi.org/10.1111/j.1365-2958.2012.08099.x
  28. Casali N., Nikolaevskyy V, Balabanova Y., Harris S., Ignatyeva O.,Kontsevaya I., Bentley D., Nejentsev S., Hoffner S., Horstmann D., BrownT, Drobnievski F. Microevolution of extensively drug-resistant tuberculosis in Russia. Genome Res. 2012; 22: 735-45. https://doi.org/10.1101/gr.128678.111
  29. Casali N., Nikolaevskyy V., Balabanova Y., Harris S., Ignatyeva O., Harris S., Bentley D., Kontsevaya I., Corander J., Bryant J., Bryant J., Nejentsev S., Hoffner S., Horstmann D., Brown T., Drobnievski F. Evolution and transmission of drug-resistant tuberculosis in a Russian population. Nat. Genet. 2014; 46: 279-86. https://doi.org/10.1038/ng.2878
  30. Sergeev R., Colijn C., Murray M., Cohen T Modeling the Dynamic Relationship Between HIV and the Risk of Drug-Resistant Tuberculosis. Science translational medicine. 2012; 4: 135-67.
  31. Comas I., Borrell S., Roetzer A. et al. Whole-genome sequencing of rifampicin-resistant Mycobacterium tuberculosis strains identifies compensatory mutations in RNA polymerase genes. Nature genetics. 2012; 44: 106-10. https://doi.org/10.1038/ng.1038
  32. Zuo T., Liu O., Gao O.Comprehensive identification of compensatory mutations in rifampicin-resistant Mycobacterium tuberculosis strains Chinese J. of tuberculosis and respiratory diseases. 2018; 12, 41 (3): 207-12. https://doi.org/10.3760/cma.j.issn.10010939.2018.03.012.
  33. Ameeruddin N., Luke E. Molecular mechanisms of action, resistance, detection to the first-line anti tuberculosis drugs: Rifampicin and pyrazinamide in the post whole genome sequencing era. Reviev Tuberculosis (Edinb). 2017; 105: 96-107. https://doi.org/10.1016/j.tube.2017.04.008.
  34. Shcherbakov D., Akbergenov R., Matt T., Sander P., Andersson D., Böttger E. Directed mutagenesis of Mycobacterium smegmatis 16S rRNA to reconstruct the in vivo evolution of aminoglycoside resistance in Mycobacterium tuberculosis. Mol. Microbiol. 2010; 77: 830-40. https://doi.org/10.1111/j.1365-2958.2010.07218.x
  35. Borrell S., Gagneux S. Infectiousness, reproductive fitness and evolution of drug-resistant Mycobacterium tuberculosis.Int J. Tuberc Lung Dis. 2009; 13: 1456-66.
  36. MacLean R.C., Vogwill T. Limits to compensatory adaptation and the persistence of antibiotic resistance in pathogenic bacteria. Evol. Med. Public Health. 2014; 2015: 4-12. https://doi.org/10.1093/emph/eou032
  37. Lange C., Abubakar I., Alffenaar C., Bothamley G.,. Caminero J., Carvalho A., Codecasa C., Crudu A., Drobniewski F., Duarte R., Erkens E., Günther G., Ibraim E., Kampmann B. Management of patients with multidrug-resistant/ extensively drug-resistant tuberculosis in Europe: a TBNET consensus statement. Eur. Respir. J. 2014; 44: 23-63. https://doi.org/10.1183/09031936.00188313
  38. Bjorkman J., Nagaev I., Berg O.G., Hughes D., Andersson D.I. Effects of environment on compensatory mutations to ameliorate costs of antibiotic resistance. Science. 2000; 287: 1479-82. https://doi.org/10.1126/science.287.5457.1479
  39. Billington O.J., McHugh T.D., Gillespie S.H. Physiological cost of rifampin resistance induced in vitro in Mycobacterium tuberculosis. Antimicrob Agents Chemother, 1999; 43: 1866-9. https://doi.org/10.1128/AAC.43.8.1866
  40. van Doorn H.R., de Haas P.E., Kremer K.F., Vandenbroucke-Grauls C.M., Borgdorff M.W., van Soolingen D.R. Public health impact of isoniazid-resistant Mycobacterium tuberculosis strains with a mutation at amino-acid position 315 of katG: a decade of experience in The Netherlands. Clin Microbiol Infect. 2006; 12: 769-75. https://doi.org/10.1111/j.1469-0691.2006.01495.x
  41. Lee J., Ammerman N., Nolan S. Isoniazid resistance without a loss of fitness in Mycobacterium tuberculosis. Nat Commun. 2012; 3: 753.
  42. Gagneux S., Long C.D., Small P.M., Van T., Schoolnik G.K., Bohannan B.J. The competitive cost of antibiotic resistance in Mycobacterium tuberculosis. Science. 2006; 312: 1944-6. https://doi.org/https://doi.org/10.1126/science.1124410.
  43. Salvatore P.P., Becerra M. Fitness costs of drug resistance mutations in multidrug-resistant Mycobacterium tuberculosis: a household-based case-control study. J. Infect. Dis. 2016; 213: 149-55. https://doi.org/10.1093/infdis/jiv347
  44. Knight G.M., Colijn C., Shrestha S., Fofana M., Cobelens F., White R.G., Dowdy D.W., Cohen T. Clin Infect Dis. 2015; 61 (3): 147-54. https://doi.org/10.1093/cid/civ579.

Supplementary files

Supplementary Files
Action
1. JATS XML
Download

This website uses cookies

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

About Cookies