REVIEW

Mycobacterium tuberculosis: drug resistance, virulence and possible solutions

About authors

1 Laboratory of Bacterial Genetics, Department of Genetics and Biotechnology,
Vavilov Institute of General Genetics of RAS, Moscow

2 Scientific Research Center for Biotechnology of Antibiotics "BIOAN", Moscow

3 Laboratory of Immunoglobulin Biosynthesis,
Mechnikov Research Institute of Vaccine and Sera, Moscow

Correspondence should be addressed: Valery N. Danilenko
Gubkina 3, Moscow, 119991; ur.ggiv@direlav

About paper

Funding: this work was supported by the Project of the Ministry of Education and Science of the Russian Federation "The role of region-specific polymorphisms of virulence genes in the formation of drug resistance of Mycobacterium tuberculosis" (Project ID RFMEFI61317X0068).

Received: 2018-06-05 Accepted: 2018-07-10 Published online: 2018-08-23
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  1. World Health Organization. Global tuberculosis report 2016. Available from: http://www.searo.who.int/tb/documents/global-tuberculosis-report-2016/en/
  2. Prozorov AA, Zaichikova MV, Danilenko VN. Mycobacterium tuberculosis mutants with multidrug resistance: History of origin, genetic and molecular mechanisms of resistance, and emerging challenges. Russian Journal of Genetics. 2012; 48 (1): 1–14.
  3. Dean AS, Cox H, Zignol M. Epidemiology of Drug-Resistant Tuberculosis. Adv Exp Med Biol. 2017; 1019: 209–20.
  4. Lange C, Chesov D, Heyckendorf J, Leung CC, Udwadia Z, Dheda K. Drug-resistant tuberculosis: An update on disease burden, diagnosis and treatment. Respirology. 2018. DOI: 10.1111/resp.13304. [Epub ahead of print].
  5. D’Costa VM, McGrann KM, Hughes DW, Wright GD. Sampling the antibiotic resistome. Science. 2006; 311 (5759): 374–7.
  6. Wright GD. The antibiotic resistome: the nexus of chemical and genetic diversity. Nat Rev Microbiol. 2007; 5 (3): 175–86.
  7. Mikheecheva NE, Zaychikova MV, Melerzanov AV, Danilenko VN. A nonsynonymous SNP catalog of Mycobacterium tuberculosis virulence genes and its use for detecting new potentially virulent sublineages. Genome Biol Evol. 2017; 9 (4): 887–99.
  8. Zaychikova MV, Zakharevich NV, Sagaidak MO, Bogolubova NA, Smirnova TG, Andreevskaya SN, et al. Mycobacterium tuberculosis Type II Toxin-Antitoxin Systems: Genetic Polymorphisms and Functional Properties and the Possibility of Their Use for Genotyping. PLoS One. 2015; 10: e0143682.
  9. Reiling N, Homolka S, Kohl TA, Steinhäuser C, Kolbe K, Schütze S, et al. Shaping the niche in macrophages: Genetic diversity of the M. tuberculosis complex and its consequences for the infected host. Int J Med Microbiol. 2017; pii: S1438–4221 (17) 30294–1.
  10. Reiling N, Homolka S, Walter K, Brandenburg J, Niwinski L, Ernst M, et al. Clade specific virulence patterns of Mycobacterium tuberculosis complex strains in human primarymacrophages and aerogenically infected mice. MBio. 2013; e00250–13.
  11. Hanekom M, Gey van Pittius NC, McEvoy C, Victor TC, Van Helden PD, Warren RM. Mycobacterium tuberculosis Beijing genotype: a template for success. Tuberculosis (Edinb). 2011; 91 (6): 510–23.
  12. Zaychikova MV, Mikheecheva NE, Belay YO, Alekseeva MG, Melerzanov AV, Danilenko VN. Single nucleotide polymorphisms of Beijing lineage Mycobacterium tuberculosis toxin-antitoxin system genes: their role in the changes of protein activity and evolution. Tuberculosis (Edinb). 2018; 112: 11–19.
  13. Ebrahimi-Rad M, Bifani P, Martin C, Kremer K, Samper S, Rauzier J, et al. Mutations in putative mutator genes of Mycobacterium tuberculosis strains of the W-Beijing family. Emerg Infect Dis. 2003; 9 (7): 838–45.
  14. Ribeiro SC, Gomes LL, Amaral EP, Andrade MR, Almeida FM, Rezende AL, et al. Mycobacterium tuberculosis strains of the modern sublineage of the Beijing family are more likely to display increased virulence than strains of the ancient sublineage. J Clin Microbiol. 2014; 52 (7): 2615–24.
  15. Kaufmann SH, Evans TG, Hanekom WA. Tuberculosis vaccines: time for a global strategy. Sci Transl Med. 2015; 7 (276): 276fs8.
  16. Chahine EB, Karaoui LR, Mansour H. Bedaquiline: a novel diarylquinoline for multidrug-resistant tuberculosis. Ann Pharmacother. 2014; 48 (1): 107–15.
  17. Bekker OB, Sokolov DN, Luzina OA, Komarova NI, Gatilov YV, Andreevskaya SN, et al. Synthesis and activity of (+)-usnic acid and (-)-usnic acid derivatives containing 1,3-thiazole cycle against Mycobacterium tuberculosis. Med Chem Res. 2015; 24 (7): 2926–38.
  18. Maslov DA, Bekker OB, Danilenko VN. New Test System for Serine/Threonine Protein Kinase Inhibitors Screening. Patent RF № 2566998, 27.10.2015.
  19. Maslov DA, Bekker OB, Alekseeva MG, Kniazeva LM, Mavletova DA, Afanasyev II, et al. Aminopyridine- and aminopyrimidine-based serine/threonine protein kinase inhibitors are drug candidates for treating drug-resistant tuberculosis. Bulletin of Russian State Medical University. 2017; 1: 38–43.
  20. Krasnov VP, Vigorov AY, Musiyak VV, Nizova IA, Gruzdev DA, Matveeva TV, et al. Synthesis and antimycobacterial activity of N-(2-aminopurin-6-yl) and N-(purin-6-yl) amino acids and dipeptides Bioorg Med Chem Lett. 2016; 26 (11): 2645–8.
  21. Sala C, Hartkoorn RC. Tuberculosis drugs: new candidates and how to find more. Future Microbiol. 2011; 6 (6): 617–33.
  22. Lechartier B, Rybniker J, Zumla A, Cole ST. Tuberculosis drug discovery in the post-post-genomic era. EMBO Mol Med. 2014; 6 (2): 158–68.
  23. Danilenko VN, Osolodkin DI, Lakatosh SA, Preobrazhenskaya MN, Shtil AA. Bacterial eukaryotic type serine-threonine protein kinases: from structural biology to targeted anti-infective drug design. Curr Top Med Chem. 2011; 11 (11): 1352–69.
  24. Cooper CB. Development of Mycobacterium tuberculosis whole cell screening hits as potential antituberculosis agents. J Med Chem. 2013; 56 (20): 7755–60.
  25. Baulard AR, Betts JC, Engohang-Ndong J, Quan S, McAdam RA, Brennan PJ, et al. Activation of the pro-drug ethionamide is regulated in mycobacteria. J Biol Chem. 2000; 275 (36): 28326–31.
  26. Willand N, Dirié B, Carette X, Bifani P, Singhal A, Desroses M, et al. Synthetic EthR inhibitors boost antituberculous activity of ethionamide. Nat Med. 2009; 15 (5): 537–44.
  27. Andries K, Verhasselt P, Guillemont J, Göhlmann HW, Neefs JM, Winkler H, et al. A diarylquinoline drug active on the ATP synthase of Mycobacterium tuberculosis. Science. 2005; 307 (5707): 223– 7.
  28. Ananthan S, Faaleolea ER, Goldman RC, Hobrath JV, Kwong CD, Laughon BE, et al. High-throughput screening for inhibitors of Mycobacterium tuberculosis H37Rv. Tuberculosis (Edinb). 2009; 89 (5): 334–53.
  29. Ballell L, Bates RH, Young RJ, Alvarez-Gomez D, Alvarez-Ruiz E, Barroso V, et al. Fueling open-source drug discovery: 177 small-molecule leads against tuberculosis. Chem Med Chem. 2013; 8 (2): 313–21.
  30. Zhang Y, Mitchison D. The curious characteristics of pyrazinamide: a review. Int J Tuberc Lung Dis. 2003; 7 (1): 6–21.
  31. Zhang Y, Chiu Chang K, Leung C-C, Wai Yew W, Gicquel B, Fallows D, et al. ‘ZS-MDR-TB’ versus ‘ZR-MDR-TB’: improving treatment of MDR-TB by identifying pyrazinamide susceptibility. Emerg Microbes Infect. 2012; 1 (7): e5.
  32. Maslov DA, Zaĭchikova MV, Chernousova LN, Shur KV, Bekker OB, Smirnova TG, et al. Resistance to pyrazinamide in Russian Mycobacterium tuberculosis isolates: pncA sequencing versus Bactec MGIT 960. Tuberculosis (Edinb). 2015; 95 (5): 608–12.
  33. Mangtani P, Abubakar I, Ariti C, Beynon R, Pimpin L, Fine PE, et al. Protection by BCG vaccine against tuberculosis: a systematic review of randomized controlled trials. Clin Infect Dis. 2014; 58 (4): 470–80.
  34. Kaufmann SH, Weiner J, von Reyn CF. Novel approaches to tuberculosis vaccine development. Int J Infect Dis. 2017; 56: 263–7.
  35. Méndez-Samperio P. Global Efforts in the Development of Vaccines for Tuberculosis: Requirements for Improved Vaccines Against Mycobacterium tuberculosis. Scand J Immunol. 2016; 84 (4): 204–10.
  36. Andersen P, Kaufmann SH. Novel vaccination strategies against tuberculosis. Cold Spring Harb Perspect Med. 2014; 4 (6). pii: a018523.
  37. Forrellad MA, Klepp L, Gioffré A, Sabioy García J, Morbidoni HR, de la Paz Santangelo M, et al. Virulence factors of the Mycobacterium tuberculosis complex. Virulence. 2013; 4 (1): 3–66.
  38. Brosch R, Gordon SV, Garnier T, Eiglmeier K, Frigui W, Valenti P, et al. Genome plasticity of BCG and impact on vaccine efficacy. Proc Natl Acad Sci USA. 2007; 104 (13): 5596–601.
  39. Uranga S, Marinova D, Martin C, Aguilo N. Protective Efficacy and Pulmonary Immune Response Following Subcutaneous and Intranasal BCG Administration in Mice. J Vis Exp. 2016; 115. DOI: 10.3791/54440.
  40. Zimmermann N, Thormann V, Hu B, Köhler AB, Imai-Matsushima A, Locht C, et al. Human isotype-dependent inhibitory antibody responses against Mycobacterium tuberculosis. EMBO Mol Med. 2016; 8 (11): 1325–39.
  41. Alvarez N, Infante JF, Borrero R, Mata D, Payan JB, Hossain MM, et al. Histopathological Study of the Lungs of Mice Receiving Human Secretory IgA and Challenged with Mycobacterium tuberculosis. Malays J Med Sci. 2014; 21 (3): 31–7.
  42. Alvarez N, Otero O, Camacho F, Borrero R, Tirado Y, Puig A, et al. Passive administration of purified secretory IgA from human colostrum induces protection against Mycobacterium tuberculosis in a murine model of progressive pulmonary infection. BMC Immunol. 2013; 14 (Suppl 1): S3.
  43. Savelkoul HFJ, Ferro VA, Strioga MM, Schijns VEJ.C. Choice and Design of Adjuvants for Parenteral and Mucosal Vaccines. Vaccines (Basel). 2015; 3 (1): 148–71.
  44. Edelman R. Vaccine adjuvants. Rev Infect Dis. 1980; 2 (3): 370–83.
  45. Pouwels PH, Leer RJ, Shaw M, Heijne den Bak-Glashouwer MJ, Tielen FD, Smit E, et al. Lactic acid bacteria as antigen delivery vehicles for oral immunization purposes. Int J Food Microbiol. 1998; 41 (2): 155–67.
  46. Bessler WG, Huber M, Baier W. Bacterial cell wall components as immunomodulators-II. The bacterial cell wall extract OM-85 BV as unspecific activator, immunogen and adjuvant in mice Int J Immunopharmacol. 1997; 19 (9–10): 551–8.
  47. López P, González-Rodríguez I, Sánchez B, Gueimonde M, Margolles A, Suárez A. Treg-inducing membrane vesicles from Bifidobacterium bifidum LMG13195 as potential adjuvants in immunotherapy. Vaccine. 2012; 30 (5): 825–9.
  48. Medina E, Talay SR, Chhatwal GS, Guzmán CA. Fibronectin-binding protein I of Streptococcus pyogenes is a promising adjuvant for antigens delivered by mucosal route. Eur J Immunol. 1998; 28 (3): 1069–77.
  49. Mizel SB, Bates JT. Flagellin as an adjuvant: cellular mechanisms and potential. J Immunol. 2010; 185 (10): 5677–82.
  50. López P, Gueimonde M, Margolles A, Suárez A. Distinct Bifidobacterium strains drive different immune responses in vitro. Int J Food Microbiol. 2010; 138 (1–2): 157–65.
  51. Caselli M, Vaira D, Cassol F, Calò G. Recombinant probiotics and their potential in human health. Int J Probiotics & Prebiotics. 2012; 7 (2): 53–8.
  52. Fedorova IA, Danilenko VN. Immunogenic properties of the probiotic component of the microbiota of the gastrointestinal tract. Biology Bulletin Reviews. 2014; 134 (2): 99–110.
  53. Medina M, Izquierdo E, Ennahar S, Sanz Y. Differential immunomodulatory properties of Bifidobacterium logum strains: relevance to probiotic selection and clinical applications. Clin Exp Immunol. 2007 Dec; 150 (3): 531–8.
  54. Khokhlova EV, Smeianov VV, Efimov BA, Kafarskaia LI, Pavlova SI, Shkoporov AN. Anti-inflammatory properties of intestinal Bifidobacterium strains isolated from healthy infants. Microbiol Immunol. 2012 Jan; 56 (1): 27–39.
  55. Averina OV, Ermolenko EI, Ratushniy AYu, Tarasova EA, Borschev YuYu, Leontieva G F, i dr. Vlijanie probiotikov na produkciju citokinov v sistemah in vitro i in vivo. Medicinskaja immunologija. 2015; 17 (5): 443–54.
  56. Barbieri N, Villena J, Herrera M, Salva S, Alvarez S. Nasally administered Lactobacillus rhamnosus accelerate the recovery of humoral immunity in B lymphocyte-deficient malnourished mice. J Nutr. 2013 Feb; 143 (2): 227–35.
  57. Tomosada Y, Chiba E, Zelaya H, Takahashi T, Tsukida K, Kitazawa H, et al. Nasally administered Lactobacillus rhamnosus strains differentially modulate respiratory antiviral immune responses and induce protection against respiratory syncytial virus infection. BMC Immunol. 2013 Aug; 15 (14): 40.
  58. Leontieva GF, Kramskaya TA, Grabovskaya KB, Philimonova VY, Layno D, Villena D, i dr. Ispol'zovanie laktobacill v kachestve ad"juvantov pri intranazal'noj immunizacii himernoj pnevmokokkovoj vakcinoj. Medicinskaja immunologija. 2016; 18 (6): 545–54.
  59. Van Overtvelt L, Moussu H, Horiot S, Samson S, Lombardi V, Mascarell L, et al. Lactic acid bacteria as adjuvants for sublingual allergy vaccines. Vaccine. 2010 Apr 9; 28 (17): 2986–92.
  60. Harata G, He F, Hiruta N, Kawase M, Kubota A, Hiramatsu M, et al. Intranasally administered Lactobacillusgasseri TMC0356 protects mice from H1N1 influenza virus infection by stimulating respiratory immune responses. World J Microbiol Biotechnol. 2011; 27 (2): 411–16.
  61. Gagneux S. Ecology and evolution of Mycobacterium tuberculosis. Nat Rev Microbiol. 2018 Apr; 16 (4): 202–13.
  62. Merker M, Blin C, Mona S, Duforet-Frebourg N, Lecher S, Willery E, et al. Evolutionary history and global spread of the Mycobacterium tuberculosis Beijing lineage. Nat Genet. 2015; 47 (3): 242–9.
  63. Mokrousov I. Insights into the Origin, Emergence, and Current Spread of a Successful Russian Clone of Mycobacterium tuberculosis. Clin Microbiol Rev. 2013; 26 (2): 342–60.
  64. Lyadova IV, Eruslanov EB, Khaidukov SV, Yeremeev VV, Majorov KB, et al. Comparative analysis of T lymphocytes recovered from the lungs of mice genetically susceptible, resistant, and hyperresistant to Mycobacterium tuberculosis-triggered disease. J Immunol. 2000 Nov 15; 165 (10): 5921–31.
  65. Zaychikova MV, Zakharevich NV, Chekalina MS, Danilenko VN. CRISPR-Сas systems of Mусоbacterium tuberculosis: the structure, evolutionary changes in different lineages, and a possible role in the promotion of virulence and resistance to drugs. Bulletin of Russian State Medical University. 2018; 2: 5–14. DOI: 10.24075/vrgmu.2018.015.
  66. Shitikov E, Bespyatykh J, Ischenko D, Alexeev D, Karpova I, Kostryukova E, et al. Unusual Large-Scale Chromosomal Rearrangements in Mycobacterium tuberculosis Beijing B0/W148 Cluster Isolates. PLoS One. 2014; 9 (1): e84971.