1887

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Volume 72, Issue 6

Unravelling the flexibility of an escape way for the bacilli No Access

Abstract

The persistence of makes it difficult to eradicate the associated infection from the host. The flexible nature of mycobacteria and their ability to adapt to adverse host conditions give rise to different drug-tolerant phenotypes. Granuloma formation restricts nutrient supply, limits oxygen availability and exposes bacteria to a low pH environment, resulting in non-replicating bacteria. These non-replicating mycobacteria, which need high doses and long exposure to anti-tubercular drugs, are the root cause of lengthy chemotherapy. Novel strategies, which are effective against non-replicating mycobacteria, need to be adopted to shorten tuberculosis treatment. This not only will reduce the treatment time but also will help prevent the emergence of multi-drug-resistant strains of mycobacteria.

  • Received:
  • Accepted:
  • Published Online:
Keyword(s): ATP homeostasis , drug resistance , granuloma , hypoxia , oxidative phosphorylation and tuberculosis
Funding
This study was supported by the:
  • Department of Biotechnology, Ministry of Science and Technology, India (Award D.O.NO.BT/HRD/35/02/2006; NO. BT/RLF/Re-entry 66/2017; GAP-39)
    • Principle Award Recipient: NITINPAL KALIA
© 2023 The Authors
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/content/journal/jmm/10.1099/jmm.0.001695
2023-06-01
2024-04-19
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References

  1. World Health Organisation Global tuberculosis report; 2022 accessed 8 March 2023
  2. Honeyborne I, Lipman M, Zumla A, McHugh TD. The changing treatment landscape for MDR/XDR-TB - Can current clinical trials revolutionise and inform a brave new world?. Int J Infect Dis 2019; 80S:S23–S28 [View Article] [PubMed]
     [Google Scholar]
  3. Vernon A, Fielding K, Savic R, Dodd L, Nahid P. The importance of adherence in tuberculosis treatment clinical trials and its relevance in explanatory and pragmatic trials. PLOS Med 2019; 16:e1002884 [View Article]
     [Google Scholar]
  4. Koul A, Arnoult E, Lounis N, Guillemont J, Andries K. The challenge of new drug discovery for tuberculosis. Nature 2011; 469:483–490 [View Article] [PubMed]
     [Google Scholar]
  5. Dheda K, Gumbo T, Maartens G, Dooley KE, McNerney R et al. The epidemiology, pathogenesis, transmission, diagnosis, and management of multidrug-resistant, extensively drug-resistant, and incurable tuberculosis. Lancet Respir Med 2017; 5:291–360 [View Article]
     [Google Scholar]
  6. Montales MT, Chaudhury A, Beebe A, Patil S, Patil N. HIV-associated TB syndemic: a growing clinical challenge worldwide. Front Public Health 2015; 3:281 [View Article] [PubMed]
     [Google Scholar]
  7. Tyagi P, Pal VK, Agrawal R, Singh S, Srinivasan S et al. Mycobacterium tuberculosis reactivates HIV-1 via exosome-mediated resetting of cellular redox potential and bioenergetics. mBio 2020; 11:e03293-19 [View Article] [PubMed]
     [Google Scholar]
  8. Mandal S, Njikan S, Kumar A, Early JV, Parish T. The relevance of persisters in tuberculosis drug discovery. Microbiology 2019; 165:492–499 [View Article]
     [Google Scholar]
  9. Goossens SN, Sampson SL, Van Rie A. Mechanisms of drug-induced tolerance in Mycobacterium tuberculosis. Clin Microbiol Rev 2020; 34:1–21 [View Article]
     [Google Scholar]
  10. Balaban NQ, Helaine S, Lewis K, Ackermann M, Aldridge B et al. Publisher correction: definitions and guidelines for research on antibiotic persistence. Nat Rev Microbiol 2019; 17:441–448 [View Article] [PubMed]
     [Google Scholar]
  11. Lee JJ, Lee S-K, Song N, Nathan TO, Swarts BM et al. Transient drug-tolerance and permanent drug-resistance rely on the trehalose-catalytic shift in Mycobacterium tuberculosis. Nat Commun 2019; 10: [View Article]
     [Google Scholar]
  12. Brauner A, Fridman O, Gefen O, Balaban NQ. Distinguishing between resistance, tolerance and persistence to antibiotic treatment. Nat Rev Microbiol 2016; 14:320–330 [View Article] [PubMed]
     [Google Scholar]
  13. Vilchèze C, Hartman T, Weinrick B, Jain P, Weisbrod TR et al. Enhanced respiration prevents drug tolerance and drug resistance in Mycobacterium tuberculosis. Proc Natl Acad Sci 2017; 114:4495–4500 [View Article]
     [Google Scholar]
  14. Hu Y, Mangan JA, Dhillon J, Sole KM, Mitchison DA et al. Detection of mRNA transcripts and active transcription in persistent Mycobacterium tuberculosis induced by exposure to rifampin or pyrazinamide. J Bacteriol 2000; 182:6358–6365 [View Article] [PubMed]
     [Google Scholar]
  15. Omollo C, Singh V, Kigondu E, Wasuna A, Agarwal P et al. Developing synergistic drug combinations to restore antibiotic sensitivity in drug-resistant Mycobacterium tuberculosis. Antimicrob Agents Chemother 2023; 65:1–13 [View Article] [PubMed]
     [Google Scholar]
  16. Ahmad Z, Klinkenberg LG, Pinn ML, Fraig MM, Peloquin CA et al. Biphasic kill curve of isoniazid reveals the presence of drug-tolerant, not drug-resistant, Mycobacterium tuberculosis in the guinea pig. J Infect Dis 2009; 200:1136–1143 [View Article] [PubMed]
     [Google Scholar]
  17. Panda A, Drancourt M, Tuller T, Pontarotti P. Genome-wide analysis of horizontally acquired genes in the genus Mycobacterium. Sci Rep 2018; 8:1–13 [View Article]
     [Google Scholar]
  18. Walter ND, Dolganov GM, Garcia BJ, Worodria W, Andama A et al. Transcriptional adaptation of drug-tolerant Mycobacterium tuberculosis during treatment of human tuberculosis. J Infect Dis 2015; 212:990–998 [View Article]
     [Google Scholar]
  19. Baek SH, Li AH, Sassetti CM. Metabolic regulation of mycobacterial growth and antibiotic sensitivity. PLoS Biol 2011; 9:e1001065 [View Article] [PubMed]
     [Google Scholar]
  20. Sharma P, Kumar B, Singhal N, Katoch VM, Venkatesan K et al. Streptomycin induced protein expression analysis in Mycobacterium tuberculosis by two-dimensional gel electrophoresis & mass spectrometry. Indian J Med Res 2010; 132:400–408 [PubMed]
     [Google Scholar]
  21. Gouzy A, Healy C, Black KA, Rhee KY, Ehrt S. Growth of Mycobacterium tuberculosis at acidic pH depends on lipid assimilation and is accompanied by reduced GAPDH activity. Proc Natl Acad Sci 2021; 118:e2024571118 [View Article] [PubMed]
     [Google Scholar]
  22. Garton NJ, Waddell SJ, Sherratt AL, Lee S-M, Smith RJ et al. Cytological and transcript analyses reveal fat and lazy persister-like bacilli in tuberculous sputum. PLoS Med 2008; 5:e75 [View Article] [PubMed]
     [Google Scholar]
  23. Martínez-Reyes I, Chandel NS. Mitochondrial TCA cycle metabolites control physiology and disease. Nat Commun 2020; 11:102 [View Article] [PubMed]
     [Google Scholar]
  24. Nguyen L. Antibiotic resistance mechanisms in M. tuberculosis: an update. Arch Toxicol 2016; 90:1585–1604 [View Article] [PubMed]
     [Google Scholar]
  25. Mailaender C, Reiling N, Engelhardt H, Bossmann S, Ehlers S et al. The MspA porin promotes growth and increases antibiotic susceptibility of both Mycobacterium bovis BCG and Mycobacterium tuberculosis. Microbiology 2004; 150:853–864 [View Article] [PubMed]
     [Google Scholar]
  26. Guo H, Courbon GM, Bueler SA, Mai J, Liu J et al. Structure of mycobacterial ATP synthase bound to the tuberculosis drug bedaquiline. Nature 2021; 589:143–147 [View Article]
     [Google Scholar]
  27. Machado D, Coelho TS, Perdigão J, Pereira C, Couto I et al. Interplay between mutations and efflux in drug resistant clinical isolates of Mycobacterium tuberculosis. Front Microbiol 2017; 8:711 [View Article] [PubMed]
     [Google Scholar]
  28. Rodrigues L, Parish T, Balganesh M, Ainsa JA. Antituberculosis drugs: reducing efflux=increasing activity. Drug Discov Today 2017; 22:592–599 [View Article] [PubMed]
     [Google Scholar]
  29. Mishra S, Shukla P, Bhaskar A, Anand K, Baloni P et al. Efficacy of β-lactam/β-lactamase inhibitor combination is linked to WhiB4-mediated changes in redox physiology of Mycobacterium tuberculosis. Elife 2017; 6:1–30 [View Article] [PubMed]
     [Google Scholar]
  30. Baker JJ, Dechow SJ, Abramovitch RB. Acid fasting: modulation of Mycobacterium tuberculosis metabolism at acidic pH. Trends Microbiol 2019; 27:942–953 [View Article] [PubMed]
     [Google Scholar]
  31. Saini V, Cumming BM, Guidry L, Lamprecht DA, Adamson JH et al. Ergothioneine maintains redox and bioenergetic homeostasis essential for drug susceptibility and virulence of Mycobacterium tuberculosis. Cell Rep 2016; 14:572–585 [View Article] [PubMed]
     [Google Scholar]
  32. Kumar A, Alam A, Bharadwaj P, Tapadar S, Rani M et al. Toxin-Antitoxin (TA) systems in stress survival and pathogenesis. Mycobacterium tuberculosis: Molecular Infection Biology, Pathogenesis, Diagnostics and New Interventions 2019257–274 [View Article]
     [Google Scholar]
  33. Slayden RA, Dawson CC, Cummings JE. Toxin-antitoxin systems and regulatory mechanisms in Mycobacterium tuberculosis. Pathog Dis 2018; 76: [View Article] [PubMed]
     [Google Scholar]
  34. Kim Y, Choi E, Hwang J. Functional studies of five toxin-antitoxin modules in Mycobacterium tuberculosis H37Rv. Front Microbiol 2016; 7:2071 [View Article] [PubMed]
     [Google Scholar]
  35. Tandon H, Sharma A, Sandhya S, Srinivasan N, Singh R. Mycobacterium tuberculosis Rv0366c-Rv0367c encodes a non-canonical PezAT-like toxin-antitoxin pair. Sci Rep 2019; 9:1163 [View Article] [PubMed]
     [Google Scholar]
  36. Gupta A, Venkataraman B, Vasudevan M, Gopinath Bankar K. Co-expression network analysis of toxin-antitoxin loci in Mycobacterium tuberculosis reveals key modulators of cellular stress. Sci Rep 2017; 7: [View Article]
     [Google Scholar]
  37. Felden B, Cattoir V. Bacterial adaptation to antibiotics through regulatory RNAs. Antimicrob Agents Chemother 2018; 62: [View Article]
     [Google Scholar]
  38. Dersch P, Khan MA, Mühlen S, Görke B. Roles of regulatory RNAs for antibiotic resistance in bacteria and their potential value as novel drug targets. Front Microbiol 2017; 8:803 [View Article] [PubMed]
     [Google Scholar]
  39. Chan H, Ho J, Liu X, Zhang L, Wong SH et al. Potential and use of bacterial small RNAs to combat drug resistance: a systematic review. Infect Drug Resist 2017; 10:521–532 [View Article] [PubMed]
     [Google Scholar]
  40. Meylan S, Andrews IW, Collins JJ. Targeting antibiotic tolerance, pathogen by pathogen. Cell 2018; 172:1228–1238 [View Article] [PubMed]
     [Google Scholar]
  41. Bigger JW. Treatment of Staphylococcal infections with penicillin by intermittent sterilisation. The Lancet 1944; 244:497–500 [View Article]
     [Google Scholar]
  42. Hobby GL, Meyer K, Chaffee E. Observations on the mechanism of action of penicillin. Exp Biol Med 1942; 50:281–285 [View Article]
     [Google Scholar]
  43. Allison KR, Brynildsen MP, Collins JJ. Heterogeneous bacterial persisters and engineering approaches to eliminate them. Curr Opin Microbiol 2011; 14:593–598 [View Article] [PubMed]
     [Google Scholar]
  44. Zhang Y, Yew WW, Barer MR. Targeting persisters for tuberculosis control. Antimicrob Agents Chemother 2012; 56:2223–2230 [View Article]
     [Google Scholar]
  45. Fisher RA, Gollan B, Helaine S. Persistent bacterial infections and persister cells. Nat Rev Microbiol 2017; 15:453–464 [View Article] [PubMed]
     [Google Scholar]
  46. Rego EH, Audette RE, Rubin EJ. Deletion of a mycobacterial divisome factor collapses single-cell phenotypic heterogeneity. Nature 2017; 546:153–157 [View Article]
     [Google Scholar]
  47. Sakatos A, Babunovic GH, Chase MR, Dills A, Leszyk J et al. Posttranslational modification of a histone-like protein regulates phenotypic resistance to isoniazid in mycobacteria. Sci Adv 2018; 4:eaao1478 [View Article] [PubMed]
     [Google Scholar]
  48. Kaushik V, Sharma S, Tiwari M, Tiwari V. Antipersister strategies against stress induced bacterial persistence. Microb Pathog 2022; 164:105423 [View Article] [PubMed]
     [Google Scholar]
  49. Nathan C. Fresh approaches to anti-infective therapies. Sci Transl Med 2012; 4:140sr2 [View Article] [PubMed]
     [Google Scholar]
  50. Ehrt S, Schnappinger D, Rhee KY. Metabolic principles of persistence and pathogenicity in Mycobacterium tuberculosis. Nat Rev Microbiol 2018; 16:496–507 [View Article] [PubMed]
     [Google Scholar]
  51. Deep A, Tiwari P, Agarwal S, Kaundal S, Kidwai S et al. Structural, functional and biological insights into the role of Mycobacterium tuberculosis VapBC11 toxin-antitoxin system: targeting a tRNase to tackle mycobacterial adaptation. Nucleic Acids Res 2018; 46:11639–11655 [View Article] [PubMed]
     [Google Scholar]
  52. Schrader SM, Vaubourgeix J, Nathan C. Biology of antimicrobial resistance and approaches to combat it. Sci Transl Med 2020; 12:eaaz6992 [View Article] [PubMed]
     [Google Scholar]
  53. Chang DPS, Guan XL. Metabolic Versatility of Mycobacterium tuberculosis during Infection and Dormancy. Metabolites 2021; 11:88 [View Article]
     [Google Scholar]
  54. Gupta VK, Kumar MM, Singh D, Bisht D, Sharma S. Drug targets in dormant Mycobacterium tuberculosis: can the conquest against tuberculosis become a reality?. Infect Dis 2018; 50:81–94 [View Article] [PubMed]
     [Google Scholar]
  55. McKinney JD, zu Bentrup KH, Muñoz-Elías EJ, Miczak A, Chen B et al. Persistence of Mycobacterium tuberculosis in macrophages and mice requires the glyoxylate shunt enzyme isocitrate lyase. Nature 2000; 406:735–738 [View Article]
     [Google Scholar]
  56. Machová I, Snašel J, Zimmermann M, Laubitz D, Plocinski P et al. Mycobacterium tuberculosis phosphoenolpyruvate carboxykinase is regulated by redox mechanisms and interaction with thioredoxin. J Biol Chem 2014; 289:13066–13078 [View Article] [PubMed]
     [Google Scholar]
  57. Barry CE, Boshoff HI, Dartois V, Dick T, Ehrt S et al. The spectrum of latent tuberculosis: rethinking the biology and intervention strategies. Nat Rev Microbiol 2009; 7:845–855 [View Article] [PubMed]
     [Google Scholar]
  58. Eoh H, Rhee KY. Multifunctional essentiality of succinate metabolism in adaptation to hypoxia in Mycobacterium tuberculosis. Proc Natl Acad Sci 2013; 110:6554–6559 [View Article]
     [Google Scholar]
  59. Eoh H, Wang Z, Layre E, Rath P, Morris R et al. Metabolic anticipation in Mycobacterium tuberculosis. Nat Microbiol 2017; 2:17084 [View Article] [PubMed]
     [Google Scholar]
  60. Wellington S, Hung DT. The expanding diversity of Mycobacterium tuberculosis drug targets. ACS Infect Dis 2018; 4:696–714 https://doi.org/10.1021/acsinfecdis.7b00255
     [Google Scholar]
  61. Vilchèze C, Jacobs WR. The isoniazid paradigm of killing, resistance, and persistence in Mycobacterium tuberculosis. J Mol Biol 2019; 431:3450–3461 [View Article] [PubMed]
     [Google Scholar]
  62. Fallow A, Domenech P, Reed MB. Strains of the East Asian (W/Beijing) lineage of Mycobacterium tuberculosis are DosS/DosT-DosR two-component regulatory system natural mutants. J Bacteriol 2010; 192:2228–2238 [View Article]
     [Google Scholar]
  63. Cho HY, Cho HJ, Kim YM, Oh JI, Kang BS. Structural insight into the heme-based redox sensing by DosS from Mycobacterium tuberculosis. J Biol Chem 2009; 284:13057–13067 [View Article] [PubMed]
     [Google Scholar]
  64. Zheng H, Colvin CJ, Johnson BK, Kirchhoff PD, Wilson M et al. Inhibitors of Mycobacterium tuberculosis DosRST signaling and persistence. Nat Chem Biol 2017; 13:218–225 [View Article] [PubMed]
     [Google Scholar]
  65. Kim M-J, Park K-J, Ko I-J, Kim YM, Oh J-I. Different roles of DosS and DosT in the hypoxic adaptation of Mycobacteria. J Bacteriol 2010; 192:4868–4875 [View Article] [PubMed]
     [Google Scholar]
  66. Converse PJ, Karakousis PC, Klinkenberg LG, Kesavan AK, Ly LH et al. Role of the dosR-dosS two-component regulatory system in Mycobacterium tuberculosis virulence in three animal models. Infect Immun 2009; 77:1230–1237 [View Article] [PubMed]
     [Google Scholar]
  67. Gautam US, Sikri K, Vashist A, Singh V, Tyagi JS. Essentiality of DevR/DosR interaction with SigA for the dormancy survival program in Mycobacterium tuberculosis. J Bacteriol 2014; 196:790–799 [View Article] [PubMed]
     [Google Scholar]
  68. Dulberger CL, Rubin EJ, Boutte CC. The mycobacterial cell envelope - a moving target. Nat Rev Microbiol 2020; 18:47–59 [View Article] [PubMed]
     [Google Scholar]
  69. Kieser KJ, Rubin EJ. How sisters grow apart: mycobacterial growth and division. Nat Rev Microbiol 2014; 12:550–562 [View Article] [PubMed]
     [Google Scholar]
  70. Velayati AA, Farnia P, Masjedi MR, Zhavnerko GK, Merza MA et al. Sequential adaptation in latent tuberculosis bacilli: observation by atomic force microscopy (AFM). Int J Clin Exp Med 2011; 4:193–199 [PubMed]
     [Google Scholar]
  71. Chuang YM, Bandyopadhyay N, Rifat D, Rubin H, Bader JS et al. Deficiency of the novel exopolyphosphatase Rv1026/PPX2 leads to metabolic downshift and altered cell wall permeability in Mycobacterium tuberculosis. mBio 2015; 6:e02428 [View Article] [PubMed]
     [Google Scholar]
  72. Torrey HL, Keren I, Via LE, Lee JS, Lewis K. High persister mutants in Mycobacterium tuberculosis. PLoS One 2016; 11:e0155127 [View Article] [PubMed]
     [Google Scholar]
  73. Jakkala K, Ajitkumar P. Hypoxic non-replicating persistent Mycobacterium tuberculosis develops thickened outer layer that helps in restricting rifampicin entry. Front Microbiol 2019; 10:2339 [View Article] [PubMed]
     [Google Scholar]
  74. Brzostek A, Pawelczyk J, Rumijowska-Galewicz A, Dziadek B, Dziadek J. Mycobacterium tuberculosis is able to accumulate and utilize cholesterol. J Bacteriol 2009; 191:6584–6591 [View Article] [PubMed]
     [Google Scholar]
  75. Baker JJ, Johnson BK, Abramovitch RB. Slow growth of Mycobacterium tuberculosis at acidic pH is regulated by phoPR and host-associated carbon sources. Mol Microbiol 2014; 94:56–69 [View Article] [PubMed]
     [Google Scholar]
  76. Feng L, Chen S, Hu Y, Stock AM. PhoPR positively regulates whiB3 expression in response to low pH in pathogenic mycobacteria. J Bacteriol 2018; 200: [View Article]
     [Google Scholar]
  77. Khan MZ, Singha B, Ali MF, Taunk K, Rapole S et al. Redox homeostasis in Mycobacterium tuberculosis is modulated by a novel actinomycete-specific transcription factor. EMBO J 2021; 40:e106111 [View Article] [PubMed]
     [Google Scholar]
  78. Rao SPS, Alonso S, Rand L, Dick T, Pethe K. The protonmotive force is required for maintaining ATP homeostasis and viability of hypoxic, nonreplicating Mycobacterium tuberculosis. Proc Natl Acad Sci 2008; 105:11945–11950 [View Article]
     [Google Scholar]
  79. Lamprecht DA, Finin PM, Rahman MA, Cumming BM, Russell SL et al. Turning the respiratory flexibility of Mycobacterium tuberculosis against itself. Nat Commun 2016; 7:12393 [View Article] [PubMed]
     [Google Scholar]
  80. Andries K, Verhasselt P, Guillemont J, Göhlmann HWH, Neefs J-M et al. A diarylquinoline drug active on the ATP synthase of Mycobacterium tuberculosis. Science 2005; 307:223–227 [View Article] [PubMed]
     [Google Scholar]
  81. Denny WA. Inhibitors of F1F0-ATP synthase enzymes for the treatment of tuberculosis and cancer. Future Med Chem 2021; 13:911–926
     [Google Scholar]
  82. Kumar S, Mehra R, Sharma S, Bokolia NP, Raina D et al. Screening of antitubercular compound library identifies novel ATP synthase inhibitors of Mycobacterium tuberculosis. Tuberculosis 2018; 108:56–63 [View Article] [PubMed]
     [Google Scholar]
  83. Swaminath S, Paul A, Pradhan A, Sebastian J, Nair RR et al. Mycobacterium smegmatis moxifloxacin persister cells produce high levels of hydroxyl radical, generating genetic resisters selectable not only with moxifloxacin, but also with ethambutol and isoniazid. Microbiology 2020; 166:180–198 [View Article] [PubMed]
     [Google Scholar]
  84. Sabir N, Hussain T, Shah SZA, Peramo A, Zhao D et al. miRNAs in tuberculosis: new avenues for diagnosis and host-directed therapy. Front Microbiol 2018; 9:602 [View Article] [PubMed]
     [Google Scholar]
  85. Tsenova L, Singhal A. Effects of host-directed therapies on the pathology of tuberculosis. J Pathol 2020; 250:636–646 [View Article] [PubMed]
     [Google Scholar]
  86. Hussain T, Zhao D, Shah SZA, Sabir N, Wang J et al. Nilotinib: a tyrosine kinase inhibitor mediates resistance to intracellular Mycobacterium via regulating autophagy. Cells 2019; 8:506 [View Article] [PubMed]
     [Google Scholar]
  87. Fatima S, Kumari A, Dwivedi VP. Advances in adjunct therapy against tuberculosis: deciphering the emerging role of phytochemicals. MedComm 2021; 2:494–513 [View Article] [PubMed]
     [Google Scholar]
  88. Darby CM, Ingólfsson HI, Jiang X, Shen C, Sun M et al. Whole cell screen for inhibitors of pH homeostasis in Mycobacterium tuberculosis. PLoS One 2013; 8:e68942 [View Article] [PubMed]
     [Google Scholar]
  89. Wayne LG, Hayes LG. An in vitro model for sequential study of shiftdown of Mycobacterium tuberculosis through two stages of nonreplicating persistence. Infect Immun 1996; 64:2062–2069 [View Article] [PubMed]
     [Google Scholar]
  90. Mapari M, Bhole RP, Khedekar PB, Chikhale RV. Challenges in targeting mycobacterial ATP synthase: the known and beyond. J Mol Struct 2022; 1247:131331 [View Article]
     [Google Scholar]
  91. Pethe K, Bifani P, Jang J, Kang S, Park S et al. Discovery of Q203, a potent clinical candidate for the treatment of tuberculosis. Nat Med 2013; 19:1157–1160 [View Article] [PubMed]
     [Google Scholar]
  92. Kalia NP, Hasenoehrl EJ, Ab Rahman NB, Koh VH, Ang MLT et al. Exploiting the synthetic lethality between terminal respiratory oxidases to kill Mycobacterium tuberculosis and clear host infection. Proc Natl Acad Sci 2017; 114:7426–7431 [View Article]
     [Google Scholar]
  93. Defraine V, Fauvart M, Michiels J. Fighting bacterial persistence: current and emerging anti-persister strategies and therapeutics. Drug Resist Updat 2018; 38:12–26 [View Article] [PubMed]
     [Google Scholar]
  94. Vilchèze C, Hartman T, Weinrick B, Jacobs WR. Mycobacterium tuberculosis is extraordinarily sensitive to killing by a vitamin C-induced Fenton reaction. Nat Commun 2013; 4:1881 [View Article] [PubMed]
     [Google Scholar]
  95. Bhusal RP, Bashiri G, Kwai BXC, Sperry J, Leung IKH. Targeting isocitrate lyase for the treatment of latent tuberculosis. Drug Discov Today 2017; 22:1008–1016 [View Article] [PubMed]
     [Google Scholar]
  96. Gandotra S, Schnappinger D, Monteleone M, Hillen W, Ehrt S. In vivo gene silencing identifies the Mycobacterium tuberculosis proteasome as essential for the bacteria to persist in mice. Nat Med 2007; 13:1515–1520 [View Article] [PubMed]
     [Google Scholar]
  97. Forrellad MA, Klepp LI, Gioffré A, Sabio y García J, Morbidoni HR et al. Virulence factors of the Mycobacterium tuberculosis complex. Virulence 2013; 4:3–66 [View Article] [PubMed]
     [Google Scholar]
  98. Goodsmith N, Guo XV, Vandal OH, Vaubourgeix J, Wang R et al. Disruption of an M. tuberculosis membrane protein causes a magnesium-dependent cell division defect and failure to persist in mice. PLoS Pathog 2015; 11:e1004645 [View Article] [PubMed]
     [Google Scholar]
  99. Goldberg MF, Saini NK, Porcelli SA. Evasion of innate and adaptive immunity by Mycobacterium tuberculosis. Molecular Genetics of Mycobacteria 2015; 747:772 [View Article]
     [Google Scholar]
  100. Dillon NA, Peterson ND, Feaga HA, Keiler KC, Baughn AD. Anti-tubercular activity of pyrazinamide is independent of trans-translation and RpsA. Sci Rep 2017; 7:6135 [View Article] [PubMed]
     [Google Scholar]
  101. Shi W, Zhang X, Jiang X, Yuan H, Lee JS et al. Pyrazinamide inhibits trans-translation in Mycobacterium tuberculosis. Science 2011; 333:1630–1632 [View Article]
     [Google Scholar]
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Unravelling the flexibility of Mycobacterium tuberculosis: an escape way for the bacilli
J. Med. Microbiol. 72, 001695 (2023); https://doi.org/10.1099/jmm.0.001695
/content/journal/jmm/10.1099/jmm.0.001695
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