Tuberculosis drug discovery in the post-post-genomic era

EMBO Molecular Medicine

Volumn 6, Issue 2, 2014, Pages 158-168

  Lechartier, Benoit ^a   Rybniker, Jan ^a,b   Zumla, Alimuddin ^c   Cole, Stewart T ^a  

^a EPFL   (Switzerland)

^b UNIVERSITY OF COLOGNE   (Germany)

^c UNIVERSITY COLLEGE LONDON HOSPITALS   (United Kingdom)

Author keywords

Drug candidates; Drug discovery; Genomics; Screening; Tuberculosis

Indexed keywords

6,7 DIHYDRO 2 NITRO 6 (4 TRIFLUOROMETHOXYBENZYLOXY) 5H IMIDAZO[2,1 B][1,3]OXAZINE; ADENOSINE TRIPHOSPHATE; BEDAQUILINE; BENZOTHIAZINONE; CYTOCHROME B; CYTOKINE; DELAMANID; DIETHYLAMINE; ETHIONAMIDE; IMATINIB; IMIDAZOPYRIDINE DERIVATIVE; ISOCITRATE LYASE; ISONIAZID; MALATE SYNTHASE; N (2 ADAMANTYL) N' GERANYLETHYLENEDIAMINE; NEW DRUG; NITROIMIDAZOLE DERIVATIVE; PANTOTHENIC ACID; PROTEIN KINASE; RIFAMPICIN; SMALL INTERFERING RNA; STREPTOMYCIN; TUBERCULOSTATIC AGENT; UNCLASSIFIED DRUG;

AMINO ACID SUBSTITUTION; BACTERIAL LOAD; CROSS RESISTANCE; DRUG DESIGN; DRUG RESEARCH; DRUG TARGETING; FLUORESCENCE MICROSCOPY; GENE EXPRESSION; GENE EXPRESSION PROFILING; GENE SEQUENCE; GENOMICS; HIGH THROUGHPUT SCREENING; IMMUNE RESPONSE; IMMUNOMODULATION; MINIMUM INHIBITORY CONCENTRATION; MISSENSE MUTATION; MYCOBACTERIUM TUBERCULOSIS; NONHUMAN; PRIORITY JOURNAL; PROTON MOTIVE FORCE; RESPIRATORY CHAIN; REVIEW; SINGLE NUCLEOTIDE POLYMORPHISM; TUBERCULOSIS; WHOLE CELL; WHOLE CELL SCREENING;

ANIMALS; ANTITUBERCULAR AGENTS; DRUG DISCOVERY; GENOMICS; HOST-PATHOGEN INTERACTIONS; HUMANS; TUBERCULOSIS; WORLD HEALTH;

EID: 84893784333     PISSN: 17574676     EISSN: 17574684     Source Type: Journal    
DOI: 10.1002/emmm.201201772     Document Type: Review

References (73)

1. Abrahams GL, Kumar A, Savvi S, Hung AW, Wen S, Abell C, Barry CE III, Sherman DR, Boshoff HI, Mizrahi V (2012a) Pathway-selective sensitization of Mycobacterium tuberculosis for target-based whole-cell screening. Chem Biol 19: 844-854
2. Abrahams KA, Cox JA, Spivey VL, Loman NJ, Pallen MJ, Constantinidou C, Fernandez R, Alemparte C, Remuinan MJ, Barros D et al (2012b) Identification of novel imidazo[1, 2-a]pyridine inhibitors targeting M. tuberculosis QcrB. PLoS One 7: e52951
3. Andries K, Verhasselt P, Guillemont J, Gohlmann HW, Neefs JM, Winkler H, Van Gestel J, Timmerman P, Zhu M, Lee E et al (2005) A diarylquinoline drug active on the ATP synthase of Mycobacterium tuberculosis. Science 307: 223-227
4. Banerjee A, Dubnau E, Quemard A, Balasubramanian V, Um KS, Wilson T, Collins D, de Lisle G, Jacobs WR Jr (1994) inhA, a gene encoding a target for isoniazid and ethionamide in Mycobacterium tuberculosis. Science 263: 227-230
5. Baulard AR, Betts JC, Engohang-Ndong J, Quan S, McAdam RA, Brennan PJ, Locht C, Besra GS (2000) Activation of the pro-drug ethionamide is regulated in mycobacteria. J Biol Chem 275: 28326-28331
6. Boshoff HI, Myers TG, Copp BR, McNeil MR, Wilson MA, Barry CE III (2004) The transcriptional responses of Mycobacterium tuberculosis to inhibitors of metabolism: novel insights into drug mechanisms of action. J Biol Chem 279: 40174-40184
7. Brodin P, Christophe T (2011) High-content screening in infectious diseases. Curr Opin Chem Biol 15: 534-539
8. Bruns H, Stegelmann F, Fabri M, Dohner K, van Zandbergen G, Wagner M, Skinner M, Modlin RL, Stenger S (2012) Abelson tyrosine kinase controls phagosomal acidification required for killing of Mycobacterium tuberculosis in human macrophages. J Immunol 189: 4069-4078
9. Bryk R, Gold B, Venugopal A, Singh J, Samy R, Pupek K, Cao H, Popescu C, Gurney M, Hotha S et al (2008) Selective killing of nonreplicating mycobacteria. Cell Host Microbe 3: 137-145
10. Christophe T, Jackson M, Jeon HK, Fenistein D, Contreras-Dominguez M, Kim J, Genovesio A, Carralot JP, Ewann F, Kim EH et al (2009) High content screening identifies decaprenyl-phosphoribose 2' epimerase as a target for intracellular antimycobacterial inhibitors. PLoS Pathog 5: e1000645
11. Cole ST, Brosch R, Parkhill J, Garnier T, Churcher C, Harris D, Gordon SV, Eiglmeier K, Gas S, Barry CE III et al (1998) Deciphering the biology of Mycobacterium tuberculosis from the complete genome sequence. Nature 393: 537-544
12. Coussens AK, Wilkinson RJ, Hanifa Y, Nikolayevskyy V, Elkington PT, Islam K, Timms PM, Venton TR, Bothamley GH, Packe GE et al (2012) Vitamin D accelerates resolution of inflammatory responses during tuberculosis treatment. Proc Natl Acad Sci USA 109: 15449-15454
13. Ehrt S, Guo XV, Hickey CM, Ryou M, Monteleone M, Riley LW, Schnappinger D (2005) Controlling gene expression in mycobacteria with anhydrotetracycline and Tet repressor. Nucleic Acids Res 33: e21
14. Fabri M, Stenger S, Shin DM, Yuk JM, Liu PT, Realegeno S, Lee HM, Krutzik SR, Schenk M, Sieling PA et al (2011) Vitamin D is required for IFN-gamma-mediated antimicrobial activity of human macrophages. Sci Transl Med 3: 104ra102
15. Ganachari M, Guio H, Zhao N, Flores-Villanueva PO (2012) Host gene-encoded severe lung TB: from genes to the potential pathways. Genes Immun 13: 605-620
16. Garcia A, Bocanegra-Garcia V, Palma-Nicolas JP, Rivera G (2012) Recent advances in antitubercular natural products. Eur J Med Chem 49: 1-23
17. Gengenbacher M, Kaufmann SH (2012) Mycobacterium tuberculosis: success through dormancy. FEMS Microbiol Rev 36: 514-532
18. Grzegorzewicz AE, Pham H, Gundi VA, Scherman MS, North EJ, Hess T, Jones V, Gruppo V, Born SE, Kordulakova J et al (2012) Inhibition of mycolic acid transport across the Mycobacterium tuberculosis plasma membrane. Nat Chem Biol 8: 334-341
19. Hartkoorn RC, Sala C, Neres J, Pojer F, Magnet S, Mukherjee R, Uplekar S, Boy-Rottger S, Altmann KH, Cole ST (2012) Towards a new tuberculosis drug: pyridomycin-nature's isoniazid. EMBO Mol Med 4: 1032-1042
20. Huitric E, Verhasselt P, Koul A, Andries K, Hoffner S, Andersson DI (2010) Rates and mechanisms of resistance development in Mycobacterium tuberculosis to a novel diarylquinoline ATP synthase inhibitor. Antimicrob Agents Chemother 54: 1022-1028
21. Hung AW, Silvestre HL, Wen S, Ciulli A, Blundell TL, Abell C (2009) Application of fragment growing and fragment linking to the discovery of inhibitors of Mycobacterium tuberculosis pantothenate synthetase. Angew Chem Int Ed Engl 48: 8452-8456
22. Jayaswal S, Kamal MA, Dua R, Gupta S, Majumdar T, Das G, Kumar D, Rao KV (2010) Identification of host-dependent survival factors for intracellular Mycobacterium tuberculosis through an siRNA screen. PLoS Pathog 6: e1000839
23. Karim AF, Chandra P, Chopra A, Siddiqui Z, Bhaskar A, Singh A, Kumar D (2011) Express path analysis identifies a tyrosine kinase Src-centric network regulating divergent host responses to Mycobacterium tuberculosis infection. J Biol Chem 286: 40307-40319
24. Kondrashov FA, Koonin EV, Morgunov IG, Finogenova TV, Kondrashova MN (2006) Evolution of glyoxylate cycle enzymes in Metazoa: evidence of multiple horizontal transfer events and pseudogene formation. Biol Direct 1: 31
25. Krieger IV, Freundlich JS, Gawandi VB, Roberts JP, Gawandi VB, Sun Q, Owen JL, Fraile MT, Huss SI, Lavandera JL et al (2012) Structure-guided discovery of phenyl-diketo acids as potent inhibitors of M. tuberculosis malate synthase. Chem Biol 19: 1556-1567
26. Kuijl C, Savage ND, Marsman M, Tuin AW, Janssen L, Egan DA, Ketema M, van den Nieuwendijk R, van den Eeden SJ, Geluk A et al (2007) Intracellular bacterial growth is controlled by a kinase network around PKB/AKT1. Nature 450: 725-730
27. Kumar D, Nath L, Kamal MA, Varshney A, Jain A, Singh S, Rao KV (2010) Genome-wide analysis of the host intracellular network that regulates survival of Mycobacterium tuberculosis. Cell 140: 731-743
28. La Rosa V, Poce G, Canseco JO, Buroni S, Pasca MR, Biava M, Raju RM, Porretta GC, Alfonso S, Battilocchio C et al (2012) MmpL3 is the cellular target of the antitubercular pyrrole derivative BM212. Antimicrob Agents Chemother 56: 324-331
29. Lebeis SL, Kalman D (2009) Aligning antimicrobial drug discovery with complex and redundant host-pathogen interactions. Cell Host Microbe 5: 114-122
30. Lew JM, Kapopoulou A, Jones LM, Cole ST (2011) TubercuList-10 years after. Tuberculosis 91: 1-7
31. Ma Z, Lienhardt C, McIlleron H, Nunn AJ, Wang X (2010) Global tuberculosis drug development pipeline: the need and the reality. Lancet 375: 2100-2109
32. Maeda K, Kosaka H, Okami Y, Umezawa H (1953) A new antibiotic, pyridomycin. J Antibiot 6: 140
33. Magnet S, Hartkoorn RC, Szekely R, Pato J, Triccas JA, Schneider P, Szantai-Kis C, Orfi L, Chambon M, Banfi D et al (2010) Leads for antitubercular compounds from kinase inhibitor library screens. Tuberculosis 90: 354-360
34. Mak PA, Rao SP, Ping Tan M, Lin X, Chyba J, Tay J, Ng SH, Tan BH, Cherian J, Duraiswamy J et al (2012) A high-throughput screen to identify inhibitors of ATP homeostasis in non-replicating Mycobacterium tuberculosis. ACS Chem Biol 7: 1190-1197
35. Makarov V, Manina G, Mikusova K, Mollmann U, Ryabova O, Saint-Joanis B, Dhar N, Pasca MR, Buroni S, Lucarelli AP et al (2009) Benzothiazinones kill Mycobacterium tuberculosis by blocking arabinan synthesis. Science 324: 801-804
36. Manjunatha U, Boshoff HI, Barry CE (2009) The mechanism of action of PA-824: novel insights from transcriptional profiling. Commun Integr Biol 2: 215-218
37. Manjunatha UH, Boshoff H, Dowd CS, Zhang L, Albert TJ, Norton JE, Daniels L, Dick T, Pang SS, Barry CE III (2006) Identification of a nitroimidazo-oxazine-specific protein involved in PA-824 resistance in Mycobacterium tuberculosis. Proc Natl Acad Sci USA 103: 431-436
38. Martineau AR, Timms PM, Bothamley GH, Hanifa Y, Islam K, Claxton AP, Packe GE, Moore-Gillon JC, Darmalingam M, Davidson RN et al (2011) High-dose vitamin D(3) during intensive-phase antimicrobial treatment of pulmonary tuberculosis: a double-blind randomised controlled trial. Lancet 377: 242-250
39. Matsumoto M, Hashizume H, Tomishige T, Kawasaki M, Tsubouchi H, Sasaki H, Shimokawa Y, Komatsu M (2006) OPC-67683, a nitro-dihydro-imidazooxazole derivative with promising action against tuberculosis in vitro and in mice. PLoS Med 3: e466
40. McKinney JD, Honer zu Bentrup K, Munoz-Elias EJ, Miczak A, Chen B, Chan WT, Swenson D, Sacchettini JC, Jacobs WR Jr, Russell DG (2000) Persistence of Mycobacterium tuberculosis in macrophages and mice requires the glyoxylate shunt enzyme isocitrate lyase. Nature 406: 735-738
41. Myler PJ, Stacy R (2012) A new drug for an old bug. Chem Biol 19: 1499-1500
42. Napier RJ, Rafi W, Cheruvu M, Powell KR, Zaunbrecher MA, Bornmann W, Salgame P, Shinnick TM, Kalman D (2011) Imatinib-sensitive tyrosine kinases regulate mycobacterial pathogenesis and represent therapeutic targets against tuberculosis. Cell Host Microbe 10: 475-485
43. Payne DJ, Gwynn MN, Holmes DJ, Pompliano DL (2007) Drugs for bad bugs: confronting the challenges of antibacterial discovery. Nat Rev Drug Discovery 6: 29-40
44. Pethe K, Bifani P, Jang J, Kang S, Park S, Ahn S, Jiricek J, Jung J, Jeon HK, Cechetto J et al (2013) Discovery of Q203, a potent clinical candidate for the treatment of tuberculosis. Nat Med 19: 1157-1160
45. Pethe K, Sequeira PC, Agarwalla S, Rhee K, Kuhen K, Phong WY, Patel V, Beer D, Walker JR, Duraiswamy J et al (2010) A chemical genetic screen in Mycobacterium tuberculosis identifies carbon-source-dependent growth inhibitors devoid of in vivo efficacy. Nat Commun 1: 57
46. Protopopova M, Hanrahan C, Nikonenko B, Samala R, Chen P, Gearhart J, Einck L, Nacy CA (2005) Identification of a new antitubercular drug candidate, SQ109, from a combinatorial library of 1, 2-ethylenediamines. J Antimicrob Chemother 56: 968-974
47. Reeves PM, Bommarius B, Lebeis S, McNulty S, Christensen J, Swimm A, Chahroudi A, Chavan R, Feinberg MB, Veach D et al (2005) Disabling poxvirus pathogenesis by inhibition of Abl-family tyrosine kinases. Nat Med 11: 731-739
48. Remuinan MJ, Perez-Herran E, Rullas J, Alemparte C, Martinez-Hoyos M, Dow DJ, Afari J, Mehta N, Esquivias J, Jimenez E et al (2013) Tetrahydropyrazolo[1, 5-a]pyrimidine-3-carboxamide and N-benzyl-6', 7'-dihydrospiro[piperidine-4, 4'-thieno[3, 2-c]pyran] analogues with bactericidal efficacy against Mycobacterium tuberculosis targeting MmpL3. PLoS One 8: e60933
49. Robertson BD, Altmann D, Barry C, Bishai B, Cole S, Dick T, Duncan K, Dye C, Ehrt S, Esmail H et al (2012) Detection and treatment of subclinical tuberculosis. Tuberculosis 92: 447-452
50. Roca FJ, Ramakrishnan L (2013) TNF dually mediates resistance and susceptibility to mycobacteria via mitochondrial reactive oxygen species. Cell 153: 521-534
51. Rosas-Taraco AG, Higgins DM, Sanchez-Campillo J, Lee EJ, Orme IM, Gonzalez-Juarrero M (2011) Local pulmonary immunotherapy with siRNA targeting TGFbeta1 enhances antimicrobial capacity in Mycobacterium tuberculosis infected mice. Tuberculosis 91: 98-106
52. Sala C, Dhar N, Hartkoorn RC, Zhang M, Ha YH, Schneider P, Cole ST (2010) Simple model for testing drugs against nonreplicating Mycobacterium tuberculosis. Antimicrob Agents Chemother 54: 4150-4158
53. Sala C, Hartkoorn RC (2011) Tuberculosis drugs: new candidates and how to find more. Future Microbiol 6: 617-633
54. Sassetti CM, Boyd DH, Rubin EJ (2003) Genes required for mycobacterial growth defined by high density mutagenesis. Mol Microbiol 48: 77-84
55. Schoeman JF, Springer P, van Rensburg AJ, Swanevelder S, Hanekom WA, Haslett PA, Kaplan G (2004) Adjunctive thalidomide therapy for childhood tuberculous meningitis: results of a randomized study. J Child Neurol 19: 250-257
56. Singh R, Manjunatha U, Boshoff HI, Ha YH, Niyomrattanakit P, Ledwidge R, Dowd CS, Lee IY, Kim P, Zhang L et al (2008) PA-824 kills nonreplicating Mycobacterium tuberculosis by intracellular NO release. Science 322: 1392-1395
57. Stanley SA, Grant SS, Kawate T, Iwase N, Shimizu M, Wivagg C, Silvis M, Kazyanskaya E, Aquadro J, Golas A et al (2012) Identification of novel inhibitors of M. tuberculosis growth using whole cell based high-throughput screening. ACS Chem Biol 7: 1377-1384
58. Stover CK, Warrener P, VanDevanter DR, Sherman DR, Arain TM, Langhorne MH, Anderson SW, Towell JA, Yuan Y, McMurray DN et al (2000) A small-molecule nitroimidazopyran drug candidate for the treatment of tuberculosis. Nature 405: 962-966
59. Subbian S, Tsenova L, O'Brien P, Yang G, Koo MS, Peixoto B, Fallows D, Dartois V, Muller G, Kaplan G (2011) Phosphodiesterase-4 inhibition alters gene expression and improves isoniazid-mediated clearance of Mycobacterium tuberculosis in rabbit lungs. PLoS Pathog 7: e1002262
60. Tahlan K, Wilson R, Kastrinsky DB, Arora K, Nair V, Fischer E, Barnes SW, Walker JR, Alland D, Barry CE III et al (2012) SQ109 targets MmpL3, a membrane transporter of trehalose monomycolate involved in mycolic acid donation to the cell wall core of Mycobacterium tuberculosis. Antimicrob Agents Chemother 56: 1797-1809
61. Tobin DM, Roca FJ, Oh SF, McFarland R, Vickery TW, Ray JP, Ko DC, Zou Y, Bang ND, Chau TT et al (2012) Host genotype-specific therapies can optimize the inflammatory response to mycobacterial infections. Cell 148: 434-446 et al.
62. Tobin DM, Vary JC Jr, Ray JP, Walsh GS, Dunstan SJ, Bang ND, Hagge DA, Khadge S, King MC, Hawn TR et al (2010) The lta4 h locus modulates susceptibility to mycobacterial infection in zebrafish and humans. Cell 140: 717-730
63. Uhlin M, Andersson J, Zumla A, Maeurer M (2012) Adjunct immunotherapies for tuberculosis. J Infect Dis 205(Suppl 2): S325-S334
64. Wang F, Sambandan D, Halder R, Wang J, Batt SM, Weinrick B, Ahmad I, Yang P, Zhang Y, Kim J et al (2013) Identification of a small molecule with activity against drug-resistant and persistent tuberculosis. Proc Natl Acad Sci USA 110: E2510-E2517
65. Wei JR, Krishnamoorthy V, Murphy K, Kim JH, Schnappinger D, Alber T, Sassetti CM, Rhee KY, Rubin EJ (2011) Depletion of antibiotic targets has widely varying effects on growth. Proc Natl Acad Sci USA 108: 4176-4181
66. Weinstein HJ, Hallett WY, Sarauw AS (1962) The absorption and toxicity of ethionamide. Am Rev Respir Dis 86: 576-578
67. Willand N, Dirie B, Carette X, Bifani P, Singhal A, Desroses M, Leroux F, Willery E, Mathys V, Deprez-Poulain R et al (2009) Synthetic EthR inhibitors boost antituberculous activity of ethionamide. Nat Med 15: 537-544
68. Wright GD (2012) Back to the future: a new 'old' lead for tuberculosis. EMBO Mol Med 4: 1029-1031
69. Young D (2009) Animal models of tuberculosis. Eur J Immunol 39: 2011-2014
70. Zhang M, Sala C, Hartkoorn RC, Dhar N, Mendoza-Losana A, Cole ST (2012) Streptomycin-starved Mycobacterium tuberculosis 18b, a drug discovery tool for latent tuberculosis. Antimicrob Agents Chemother 56: 5782-5789
71. Zhang Y, Yew WW (2009) Mechanisms of drug resistance in Mycobacterium tuberculosis. Int J Tuberc Lung Dis 13: 1320-1330
72. Zumla A, Nahid P, Cole ST (2013a) Advances in the development of new tuberculosis drugs and treatment regimens. Nat Rev Drug Discovery 12: 388-404
73. Zumla A, Raviglione M, Hafner R, von Reyn CF (2013b) Tuberculosis. New Engl J Med 368: 745-755