Molecular bases of the interaction of Mycobacteria tuberculosis complex and anti-tuberculosis drugs: Current state of the problem and its epidemiological significance

Cover Page


Cite item

Full Text

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

Abstract

According to the World Health Organization Global Tuberculosis Report, published in 2022, tuberculosis and its drug-resistant forms are on the rise for the first time in recent years. The ability to become immune to anti-tuberculosis drugs is a fundamental feature of the tuberculosis agent. In some cases, tuberculosis develops a transient resistance to antibacterial drugs based on a combination of adaptive biological properties of the mycobacterium without altering the genetic apparatus. This phenomenon is called drug-induced tolerance. Its development is associated with the slowing or altering of bacterial metabolism, increasing the thickness of the cell wall, activation of specific molecular pumps, and removal of medicinal substances from outside the cell. The same and some other mechanisms are involved in the development of another phenomenon — drug resistance, which is associated with inherited changes in the genetic apparatus of mycobacterium. The review is devoted to the molecular bases of the interaction of mycobacterium tuberculosis with anti-tuberculosis drugs and its epidemiological significance.

Full Text

Restricted Access

About the authors

Yuri N. Khomyakov

Central Research Institute of Epidemiology

Author for correspondence.
Email: khomyakovyuri@yandex.ru
ORCID iD: 0000-0003-0540-252X
SPIN-code: 2405-6712

MD, Dr. Sci. (Biol.), Cand. Sci. (Med.)

Russian Federation, Moscow

Darya D. Zvyagintseva

Central Research Institute of Epidemiology

Email: dzvyaginceva@gmail.com
ORCID iD: 0009-0009-6978-9226
Russian Federation, Moscow

Tatiana I. Khomyakova

Research Institute of Human Morphology of Russian Scientific Center of Surgery

Email: tathkom@yandex.ru
ORCID iD: 0000-0003-3451-1952
SPIN-code: 5059-1414

MD, Cand. Sci. (Med.)

Russian Federation, Moscow

References

  1. Paulson T. Epidemiology: a mortal foe. Nature. 2013;502(7470): S2–S3. doi: https://doi.org/10.1038/502S2a
  2. Global tuberculosis report 2022. Geneva: World Health Organization; 2022. 52 p.
  3. Global Action Plan on Antimicrobial Resistance. Geneva: World Health Organization; 2016. 32 p. URL: https://www.who.int/publications/i/item/9789241509763.
  4. Hatfull GF. Actinobacteriophages: Genomics, Dynamics, and Applications. Annu Rev Virol. 2020;7(1):37–61. doi: 10.1146/annurev-virology-122019-070009
  5. Gagneux S. Ecology and evolution of Mycobacterium tuberculosis. Nat Rev Microbiol. 2018;16(4):202–213. doi: 10.1038/nrmicro.2018.8
  6. Comas I, Coscolla M, Luo T, et al. Out-of-Africa migration and Neolithic coexpansion of Mycobacterium tuberculosis with modern humans. Nat Genet. 2013;45(10):1176–1182. doi: 10.1038/ng.2744
  7. Coscolla M, Gagneux S. Consequences of genomic diversity in Mycobacterium tuberculosis. Semin Immunol. 2014;26(6):431–444. doi: 10.1016/j.smim.2014.09.012
  8. Coscolla M, Gagneux S, Menardo F, et al. Phylogenomics of Mycobacterium africanum reveals a new lineage and a complex evolutionary history. Microb Genom. 2021;7(2):000477. doi: 10.1099/mgen.0.000477
  9. Holt KE, McAdam P, Thai PVK, et al. Frequent transmission of the Mycobacterium tuberculosis Beijing lineage and positive selection for the EsxW Beijing variant in Vietnam. Nat Genet. 2018;50(6): 849–856. doi: 10.1038/s41588-018-0117-9
  10. Firdessa R, Berg S, Hailu E, et al. Mycobacterial lineages causing pulmonary and extrapulmonary tuberculosis, Ethiopia. Emerg Infect Dis. 2013;19(3):460–463. doi: 10.3201/eid1903.120256
  11. Ford CB, Shah RR, Maeda MK, et al. Mycobacterium tuberculosis mutation rate estimates from different lineages predict substantial differences in the emergence of drug-resistant tuberculosis. Nat Genet. 2013;45(7):784–790. doi: 10.1038/ng.2656
  12. Goossens SN, Sampson SL, Van Rie A. Mechanisms of Drug-Induced Tolerance in Mycobacterium tuberculosis. Clin Microbiol Rev. 2020;34(1):e00141-20. doi: 10.1128/CMR.00141-20
  13. Grace AG, Mittal A, Jain S, et al. Shortened treatment regimens versus the standard regimen for drug-sensitive pulmonary tuberculosis. Cochrane Database Systematic Review. 2018(1): CD012918. doi: 10.1002/14651858.CD012918
  14. Rossiiskoe obshchestvo ftiziatrov, Assotsiatsiya ftiziatrov. Tuberculosis in adults. Clinical guidelines. Мoscow; 2022. 151 p. (In Russ).
  15. Akalu T, Muchie K, Muchie G. Time to sputum culture conversion and its determinants among Multi-drug resistant Tuberculosis patients at public hospitals of the Amhara Regional State: A multicenter retrospective follow up study. PLoS One. 2018;13(6):e0199320. doi: 10.1371/journal.pone.0199320
  16. Boeree MJ, Heinrich N, Aarnoutse R, et al. High-dose rifampicin, moxifloxacin, and SQ109 for treating tuberculosis: a multi-arm, multi-stage randomised controlled trial. Lancet Infect Dis. 2017;17:39–49. doi: 10.1016/S1473-3099(16)30274-2
  17. Afzal A, Rathore R, Butt NF, et al. Efficacy of vitamin D supplementation in achieving an early Sputum Conversion in Smear positive Pulmonary Tuberculosis. Pak J Med Sci. 2018;34:849–854. doi: 10.12669/pjms.344.14397
  18. Musteikienė G, Miliauskas S, Zaveckienė J, et al. Factors associated with sputum culture conversion in patients with pulmonary tuberculosis. Medicina (Kaunas). 2017;53(6):386–393. doi: 10.1016/j.medici.2018.01.005
  19. Barr DA, Kamdolozi M, Nishihara Y, et al. Serial image analysis of Mycobacterium tuberculosis colony growth reveals a persistent subpopulation in sputum during treatment of pulmonary TB. Tuberculosis (Edinb). 2016;98:110–115. doi: 10.1016/j.tube.2016.03.001
  20. Burger DA, Schall R. Robust fit of Bayesian mixed effects regression models with application to colony forming unit count in tuberculosis research. Stat Med. 2018;37(4):544–556. doi: 10.1002/sim.7529
  21. Balaban NQ, Helaine S, Lewis K, et al. Definitions and guidelines for research on antibiotic persistence. Nat Rev Microbiol. 2019;17(7):441–448. doi: 10.1038/s41579-019-0196-3
  22. Trastoy R, Manso T, Fernandez-Garcia L, et al. Mechanisms of bacterial tolerance and persistence in the gastrointestinal and respiratory environments. Clin Microbiol Rev. 2018;31(4):e00023-18. doi: 10.1128/CMR.00023-18
  23. Gollan B, Grabe G, Michaux C, Helaine S. Bacterial persisters and infection: past, present, and progressing. Annu Rev Microbiol. 2019;73:359–385. doi: 10.1146/annurev-micro-020518-115650
  24. Hegde SR. Computational identification of the proteins associated with quorum sensing and biofilm formation in Mycobacterium tuberculosis. Front Microbiol. 2020;10:3011. doi: 10.3389/fmicb.2019.03011
  25. Brauner A, Fridman O, Gefen O, et al. Distinguishing between resistance, tolerance and persistence to antibiotic treatment. Nat Rev Microbiol. 2016;14(5):320−330. doi: 10.1038/nrmicro.2016.34
  26. Khawbung JL, Nath D, Chakraborty S. Drug resistant Tuberculosis: A review. Comp Immunol Microbiol Infect Dis. 2021;74:101574. doi: 10.1016/j.cimid.2020.101574
  27. Briffotaux J, Liu S, Gicquel B. Genome-wide Transcriptional Responses of Mycobacterium to Antibiotics. Front Microbiol. 2019; 1(10):249. doi: 10.3389/fmicb.2019.00249
  28. Walter ND, Dolganov GM, Garcia BJ, et al. Transcriptional adaptation of drug-tolerant Mycobacterium tuberculosis during treatment of human tuberculosis. J Infect Dis. 2015;212(6):990–998. doi: 10.1093/infdis/jiv149
  29. Zhou P, Wang X, Wang Z, et al. Sigma factors mediated signaling in Mycobacterium tuberculosis. Future Microbiol. 2018;13:231–240. doi: 10.2217/fmb-2017-0127
  30. Miryala SK, Anbarasu A, Ramaiah S. Impact of bedaquiline and capreomycin on the gene expression patterns of multidrug-resistant Mycobacterium tuberculosis H37Rv strain and understanding the molecular mechanism of antibiotic resistance. J Cell Biochem. 2019;120(9):14499–14509. doi: 10.1002/jcb.28711
  31. Kumar A, Alam A, Bharadwaj P, et al. Toxin-antitoxin (TA) systems in stress survival and pathogenesis. In: Hasnain S, Ehtesham N, Grover S, editors. Mycobacterium tuberculosis: molecular infection biology, pathogenesis, diagnostics and new interventions. New Delhi: Springer; 2019. P. 257–274. doi: 10.1007/978-981-32-9413-4_15
  32. Slayden RA, Dawson CC, Cummings JE. Toxin-antitoxin systems and regulatory mechanisms in Mycobacterium tuberculosis. Pathog Dis. 2018;76(4):fty039. doi: 10.1093/femspd/fty039
  33. Tandon H, Sharma A, Sandhya S, et al. Mycobacterium tuberculosis Rv0366c-Rv0367c encodes a non-canonical PezAT-like toxin-antitoxin pair. Sci Rep. 2019;9(1):1163. doi: 10.1038/s41598-018-37473-у
  34. Gerrick ER, Barbier T, Chase MR, et al. Small RNA profiling in Mycobacterium tuberculosis identifies MrsI as necessary for an anticipatory iron sparing response. Proc Natl Acad Sci. U S A. 2018;115(25):6464–6469. doi: 10.1073/pnas.1718003115
  35. Machado D, Coelho T, Perdigão J, et al. Interplay between Mutations and Efflux in Drug Resistant Clinical Isolates of Mycobacterium tuberculosis. Front Microbiol. 2017;8:711. doi: 10.3389/fmicb.2017.00711
  36. Li G, Zhang J, Guo Q, et al. Efflux pump gene expression in multidrug-resistant Mycobacterium tuberculosis clinical isolates. PLoS One. 2015;10:e0119013. doi: 10.1371/journal.pone.0119013
  37. Hicks N, Yang J, Zhang X, et al. Clinically prevalent mutations in Mycobacterium tuberculosis alter propionate metabolism and mediate multidrug tolerance. Nat Microbiol. 2018;3:1032–1042. doi: 10.1038/s41564-018-0218-3
  38. Catalogue of mutations in Mycobacterium tuberculosis complex and their association with drug resistance. Geneva: World Health Organization; 2021. 85 p.
  39. Zaw M, Emran N, Lin Z. Mutations inside rifampicin-resistance determining region of rpoB gene associated with rifampicin-resistance in Mycobacterium tuberculosis. J Infect Public Health. 2018;11(5):605–610. doi: 10.1016/j.jiph.2018.04.005
  40. Louw GE, Warren RM, Gey van Pittius NC, et al. Rifampicin reduces susceptibility to ofloxacin in rifampicin-resistant Mycobacterium tuberculosis through efflux. Am J Respir Crit Care Med. 2011;184:269–276. doi: 10.1164/rccm.201011-1924OC
  41. Zhu JH, Wang BW, Pan M, et al. Rifampicin can induce antibiotic tolerance in mycobacteria via paradoxical changes in rpoB transcription. Nat Commun. 2018;9(1):4218. doi: 10.1038/s41467-018-06667-3
  42. Javid B, Sorrentino F, Toosky M, et al. Mycobacterial mistranslation is necessary and sufficient for rifampicin phenotypic resistance. Proc Natl Acad Sci U S A. 2014;111(3):1132–1137. doi: 10.1073/pnas.1317580111
  43. Zhang L, Zhao Y, Gao Y, et al. Structures of cell wall arabinosyltransferases with the anti-tuberculosis drug ethambutol. Science. 2020;368(6496):1211–1219. doi: 10.1126/science.aba9102
  44. Zhu C, Liu Y, Hu L, et al. Molecular mechanism of the synergistic activity of ethambutol and isoniazid against Mycobacterium tuberculosis. J Biol Chem. 2018;293(43):16741–16750. doi: 10.1074/jbc.RA118.002693
  45. Pisu D, Provvedi R, Espinosa DM, et al. The alternative sigma factors SigE and SigB are involved in tolerance and persistence to antitubercular drugs. Antimicrob Agents Chemother. 2017;61: e01596-17. doi: 10.1128/AAC.01596-17
  46. Diacon AH, Dawson R, von Groote-Bidlingmaier F, et al. 14-day bactericidal activity of PA-824, bedaquiline, pyrazinamide, and moxifloxacin combinations: a randomised trial. Lancet. 2012; 380(9846):986–993. doi: 10.1016/S0140-6736(12)61080-0
  47. Koul A, Vranckx L, Dhar N, et al. Delayed bactericidal response of Mycobacterium tuberculosis to bedaquiline involves remodelling of bacterial metabolism. Nat Commun. 2014;5:3369. doi: 10.1038/ncomms4369
  48. Peterson EJR, Ma S, Sherman DR, et al. Network analysis identifies Rv0324 and Rv0880 as regulators of bedaquiline tolerance in Mycobacterium tuberculosis. Nat Microbiol. 2016;1(8):16078. doi: 10.1038/nmicrobiol.2016.78
  49. Liu J, Gefen O, Ronin I, et al. Effect of tolerance on the evolution of antibiotic resistance under drug combinations. Science. 2020;367:200–204. doi: 10.1126/science.aay3041
  50. Levin-Reisman I, Ronin I, Gefen O, et al. Antibiotic tolerance facilitates the evolution of resistance. Science. 2017;355(6327): 826–830. doi: 10.1126/science.aaj2191
  51. Lee JJ, Lee SK, Song N, et al. Transient drug-tolerance and permanent drug-resistance rely on the trehalose-catalytic shift in Mycobacterium tuberculosis. Nat Commun. 2019;10(1):2928. doi: 10.1038/s41467-019-10975-7
  52. Mishra R, Kohli S, Malhotra N, et al. Targeting redox heterogeneity to counteract drug tolerance in replicating Mycobacterium tuberculosis. Sci Transl Med. 2019;11(518):eaaw6635. doi: 10.1126/scitranslmed.aaw6635
  53. Gopal P, Gruber G, Dartois V, et al. Pharmacological and Molecular Mechanisms Behind the Sterilizing Activity of Pyrazinamide. Trends Pharmacol Sci. 2019;4:930–940. doi: 10.1016/j.tips.2019.10.005
  54. Conradie F, Diacon AH, Ngubane N. Treatment of Highly Drug-Resistant Pulmonary Tuberculosis. N Engl J Med. 2020. 382;10:893–902. doi: 10.1056/NEJMoa1901814
  55. Vashisht R, Bhat AG, Kushwaha S, et al. Systems level mapping of metabolic complexity in Mycobacterium tuberculosis to identify high-value drug targets. J Transl Med. 2014;12:263. doi: 10.1186/s12967-014-0263-5
  56. Pule CM, Sampson SL, Warren RM. et al. Efflux pump inhibitors: targeting mycobacterial efflux systems to enhance TB therapy. J Antimicrob Chemother. 2016;71(1):17–26. doi: 10.1093/jac/dkv316
  57. Naumov AG, Pavlunin AV. Mechanisms of development of medicine stability Mycobacterium tuberculosis: is there a chance to win? Pul’monologiya. 2021;31(1):100–108. (in Russ). doi: 10.18093/0869-0189-2021-31-1-100-10
  58. Mishin VYu, Zavrazhnov SP, Mitronin AV, Grigor’ev YuG. Ftiziatriya: uchebnik dlya meditsinskikh vuzov. 2nd ed., revised and expanded. Мoscow: GEOTAR-Media; 2016. (In Russ).
  59. Vorobjeva ОА. Tuberculous mycobacteria drug resistance — the present view on the problem. Sibirskii meditsinskii zhurnal. 2008;(2):5–8. (In Russ).
  60. Torres Ortiz A, Coronel J, Vidal JR, et al. Genomic signatures of pre-resistance in Mycobacterium tuberculosis. Nat Commun. 2021;12(1):7312. doi: 10.1038/S41467-021-27616-7
  61. Li J, Gao X, Luo T, et al. Association of gyrA/B mutations and resistance levels to fluoroquinolones in clinical isolates of Mycobacterium tuberculosis. Emerg Microbes Infect. 2014;3(1):1–5. doi: 10.1038/emi.2014.21
  62. Chernyaeva EN. Biochemical mechanisms of Mycobacterium tuberculosis drug resistance. Vestnik SPbGU. 2012;3(2):77–91. (In Russ).
  63. Fisenko VP. Protivotuberkuleznye sredstva: printsipy deistviya, pobochnye effekty i perspektivy sozdaniya novykh lekarstvennykh preparatov. Vrach. 2006;(12):30–34. (In Russ).
  64. Mozhokina GN, Samoylova AG, Vasilyeva IA. The problem of neurotoxicity of drugs in the treatment of tuberculosis patients. Tuberculosis and Lung Diseases. 2020;98(10):58–63. (In Russ). doi: 10.21292/2075-1230-2020-98-10-58-63
  65. Mozhokina GN, Samoylova AG, Zangieva ZA Nephrotoxic characteristics of anti-tuberculosis drugs. Tuberculosis and Lung Diseases. 2019;97(10):59–65. (In Russ). doi: 10.21292/2075-1230-2019-97-10-59-65
  66. Starshinova AA, Pavlova MV, Yablonskiy PK, et al. Evolution of phthisiatry — a search for new methods and drugs effective for the treatment of tuberculosis. Prakticheskaya meditsina. 2014;83(7): 133–139. (In Russ).
  67. Zhang Y, Shi W, Zhang W, Mitchison D. Mechanisms of Pyrazinamide Action and Resistance. Microbiol Spectr. 2014;2(4): MGM2-0023-2013. doi: 10.1128/microbiolspec.MGM2-0023-2013
  68. Sysoev PG, Lyukina AN, Madatova MK. Evolyutsiya protivotuberkuleznykh preparatov. Modern science. 2020;5(1): 263–267. (In Russ).
  69. Burmistrova IА, Samoylova АО, Tyulkova TE, et al. Drug resistance of M. tuberculosis (historical aspects, current level of knowledge). Tuberculosis and Lung Diseases. 2020;98(1):54–61. (In Russ). doi: 10.21292/2075-1230-2020-98-1-54-61
  70. Desjardins C, Cohen K, Munsamy V, et al. Genomic and functional analyses of Mycobacterium tuberculosis strains implicate ald in D-cycloserine resistance. Nat Genet. 2016;48:544–551. doi: 10.1038/ng.3548
  71. Ruzanov DY, Skriagina AM, Buinevich IV, et al. New regimens and new medications in the treatment of tuberculosis: keeping step? Clinical Microbiology and Antimicrobial Chemotherapy. 2021;(1): 27–42. doi: 10.36488/cmac.2021.1.27-42
  72. Vyazovaya AA, Akhmedova GM, Gerasimova AA, et al. Perchlozone resistance mutations in serial isolates of Mycobacterium tuberculosis. Problems in Medical Mycology. 2020;(3):63–64. (In Russ).
  73. Khoshnood S, Goudarzi M, Taki E, et al. Bedaquiline: Current status and future perspectives. J Glob Antimicrob Resist. 2021;25: 48–59. doi: 10.1016/J.Jgar.2021.02.017
  74. Chesov E, Chesov D, Maurer FP, et al. Emergence of bedaquiline-resistance in a highburden country of tuberculosis. Eur Respir J. 2022;59(3):2100621. doi: 10.1183/13993003.00621-2021
  75. Gomez-Gonzalez P, Perdigao J, Gomes P, et al. Genetic diversity of candidate loci linked to Mycobacterium tuberculosis resistance to bedaquiline, delamanid and pretomanid. Sci Rep. 2021;11(1):19431. doi: 10.1038/S41598-021-98862-4
  76. Zimenkov DV, Nosova EYu, Kulagina EV, et al. Molekulyarnye mekhanizmy ustoichivosti Mycobacterium tuberculosis k bedakvilinu i linezolidu. Molekulyarnaya diagnostika. 2017;1:496–497. (In Russ).
  77. Peretokina IV, Krylova LU, Antonova OV, et al. Reduced susceptibility and resistance to bedaquiline in clinical M. tuberculosis isolates. J Infect. 2020;80(5):527–535. doi: 10.1016/j.jinf.2020.01.007
  78. Hashemian SMR, Farhadi T, Ganjparvar M. Linezolid: a review of its properties, function, and use in critical care. Drug Des Devel Ther. 2018;12:1759–1767. doi: 10.2147/DDDT.S164515
  79. Fortun J, Marti-Davila P, Navas E, et al. Linezolid for the treatment of multidrug-resistant tuberculosis. J Antimicrob Chemother. 2005;56(1):180–185. doi: 10.1093/jac/dki148
  80. Vasil’eva IA, Samoilova AG, Zimina VN, et al. Experience with linezolid used in the combination treatment of patients with tuberculosis with broad drug resistance in the pathogen. Tuberculosis and Lung Diseases. 2011;88(3):17–20. (In Russ.).
  81. Richter E, Rusch-Gerdes S, Hillemann D. First Linezolid-Resistant Clinical Isolates of Mycobacterium tuberculosis. Antimicrob Agents Chemother. 2007;51(4):1534–1536. doi: 10.1128/AAC.01113-06
  82. Zimina VN, Viktorova IB. Delamanid is a new anti-tuberculosis drug: use, limitations, and prospects. Tuberculosis and Lung Diseases. 2021;99(2):58–66. (In Russ). doi: 10.21292/2075-1230-2021-99-2-58-66
  83. Park S, Jung J, Kim J, et al. Investigation of Clofazimine Resistance and Genetic Mutations in Drug-Resistant Mycobacterium tuberculosis Isolates. J Clin Med. 2022;11(7):1927. doi: 10.3390/jcm11071927.3390/jcm11071927
  84. WHO consolidated guidelines on drug-resistant tuberculosis treatment. Copenhagen: WHO Regional Office for Europe; 2019. 117 p. (In Russ).
  85. Guerrero-Bustamante CA, Dedrick RM, Garlena RA, et al. Toward a Phage Cocktail for Tuberculosis: Susceptibility and Tuberculocidal Action of Mycobacteriophages against Diverse Mycobacterium tuberculosis. mBio. 2021;12(3):e00973-21. doi: 10.1128/mBio.00973-21

Supplementary files

Supplementary Files
Action
1. JATS XML
Download

Copyright (c) 2023 Eco-vector


СМИ зарегистрировано Федеральной службой по надзору в сфере связи, информационных технологий и массовых коммуникаций (Роскомнадзор).
Регистрационный номер и дата принятия решения о регистрации СМИ: № 014448 от 08.02.1996. 
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 ЭЛ № ФС 77 - 80652 от 15.03.2021 .


This website uses cookies

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

About Cookies