Emerging Approaches to Tuberculosis Drug Development: At Home in the Metabolome

Trends in Pharmacological Sciences

Volumn 38, Issue 4, 2017, Pages 393-405

  Jansen, Robert S ^a   Rhee, Kyu Y ^a  

^a WEILL CORNELL MEDICAL COLLEGE   (United States)

Author keywords

drug development; metabolomics; tuberculosis

Indexed keywords

ISONIAZID; RIFAMPICIN; STREPTOMYCIN; SULFAMETHOXAZOLE; SULFONAMIDE; TUBERCULOSTATIC AGENT;

ANTIBIOTIC RESISTANCE; BACTERIAL GENOME; BACTERIAL INFECTION; BACTERIAL VIRULENCE; BIOCHEMISTRY; DRUG USE; GENETICS; HIGH THROUGHPUT SCREENING; IN VITRO STUDY; IN VIVO STUDY; INFECTION CONTROL; METABOLOME; METABOLOMICS; MICROBIOLOGY; MUTAGENESIS; MYCOBACTERIUM BOVIS; MYCOBACTERIUM TUBERCULOSIS; NONHUMAN; OXIDATIVE STRESS; PHARMACODYNAMICS; REVIEW; STRUCTURE ACTIVITY RELATION; CLASSIFICATION; DRUG DEVELOPMENT; HUMAN;

ANTITUBERCULAR AGENTS; DRUG DISCOVERY; DRUG RESISTANCE, MICROBIAL; HUMANS; METABOLOMICS;

EID: 85011295947     PISSN: 01656147     EISSN: 18733735     Source Type: Journal    
DOI: 10.1016/j.tips.2017.01.005     Document Type: Review

References (80)

1. 1 Davies, J., Davies, D., Origins and evolution of antibiotic resistance. Microbiol. Mol. Biol. Rev. 74 (2010), 417–433.
2. 2 Fiehn, O., Metabolomics – the link between genotypes and phenotypes. Plant Mol. Biol. 48 (2002), 155–171.
3. 3 Patti, G.J., et al. Innovation: metabolomics: the apogee of the omics trilogy. Nat. Rev. Mol. Cell Biol. 13 (2012), 263–269.
4. 4 Galván-Peña, S., O'Neill, L.A.J., Metabolic reprograming in macrophage polarization. Front. Immunol., 5, 2014, 420.
5. 5 World Health Organization. Global Tuberculosis Report 2016, 2016. WHO.
6. 6 Lu, L.L., et al. A functional role for antibodies in tuberculosis. Cell, 167, 2016 433–443.e14.
7. 7 Horsburgh, C.R.J., et al. Treatment of tuberculosis. N. Engl. J. Med. 373 (2015), 2149–2160.
8. 8 Zumla, A., et al. Advances in the development of new tuberculosis drugs and treatment regimens. Nat. Rev. Drug Discov. 12 (2013), 388–404.
9. 9 Chakraborty, S., Rhee, K.Y., Tuberculosis drug development: history and evolution of the mechanism-based paradigm. Cold Spring Harb. Perspect. Med., 5, 2015, a021147.
10. 10 Nathan, C., Cooperative development of antimicrobials: looking back to look ahead. Nat. Rev. Microbiol. 13 (2015), 651–657.
11. 11 Lindsay, M.A., Target discovery. Nat. Rev. Drug Discov. 2 (2003), 831–838.
12. 12 Marchetti, C., et al. Fragment-based approaches to TB drugs. Parasitology, 2016, 10.1017/S0031182016001876 Published online November 2, 2016.
13. 13 Scott, D.E., et al. Fragment-based approaches in drug discovery and chemical biology. Biochemistry (Mosc.) 51 (2012), 4990–5003.
14. 14 Savarino, A., A historical sketch of the discovery and development of HIV-1 integrase inhibitors. Expert Opin. Investig. Drugs 15 (2006), 1507–1522.
15. 15 Lechartier, B., et al. Tuberculosis drug discovery in the post-post-genomic era. EMBO Mol. Med. 6 (2014), 158–168.
16. 16 Saghatelian, A., et al. Assignment of endogenous substrates to enzymes by global metabolite profiling. Biochemistry (Mosc.) 43 (2004), 14332–14339.
17. 17 Hopkins, A.L., Groom, C.R., The druggable genome. Nat. Rev. Drug Discov. 1 (2002), 727–730.
18. 18 Cole, S.T., et al. Deciphering the biology of Mycobacterium tuberculosis from the complete genome sequence. Nature 393 (1998), 537–544.
19. 19 Sassetti, C.M., Rubin, E.J., Genetic requirements for mycobacterial survival during infection. Proc. Natl. Acad. Sci. U. S. A. 100 (2003), 12989–12994.
20. 20 Sassetti, C.M., et al. Comprehensive identification of conditionally essential genes in mycobacteria. Proc. Natl. Acad. Sci. U. S. A. 98 (2001), 12712–12717.
21. 21 Ansong, C., et al. Identification of widespread adenosine nucleotide binding in Mycobacterium tuberculosis. Chem. Biol. 20 (2013), 123–133.
22. 22 Ortega, C., et al. Systematic survey of serine hydrolase activity in Mycobacterium tuberculosis defines changes associated with persistence. Cell Chem. Biol. 23 (2016), 290–298.
23. 23 Berney, M., et al. Essential roles of methionine and S-adenosylmethionine in the autarkic lifestyle of Mycobacterium tuberculosis. Proc. Natl. Acad. Sci. U. S. A. 112 (2015), 10008–10013.
24. 24 Gouzy, A., et al. Mycobacterium tuberculosis nitrogen assimilation and host colonization require aspartate. Nat. Chem. Biol. 9 (2013), 674–676.
25. 25 Gouzy, A., et al. Mycobacterium tuberculosis exploits asparagine to assimilate nitrogen and resist acid stress during infection. PLoS Pathog., 10, 2014, e1003928.
26. 26 Trujillo, C., et al. Triosephosphate isomerase is dispensable in vitro yet essential for Mycobacterium tuberculosis to establish infection. mBio, 5, 2014, e00085.
27. 27 Ehebauer, M.T., et al. Characterization of the mycobacterial acyl-CoA carboxylase holo complexes reveals their functional expansion into amino acid catabolism. PLoS Pathog., 11, 2015, e1004623.
28. 28 McKinney, J.D., et al. Persistence of Mycobacterium tuberculosis in macrophages and mice requires the glyoxylate shunt enzyme isocitrate lyase. Nature 406 (2000), 735–738.
29. 29 Muñoz-Elías, E.J., McKinney, J.D., Mycobacterium tuberculosis isocitrate lyases 1 and 2 are jointly required for in vivo growth and virulence. Nat. Med. 11 (2005), 638–644.
30. 30 Eoh, H., Rhee, K.Y., Methyl citrate cycle defines the bactericidal essentiality of isocitrate lyase for survival of Mycobacterium tuberculosis on fatty acids. Proc. Natl. Acad. Sci. U. S. A. 111 (2014), 4976–4981.
31. 31 Venugopal, A., et al. Virulence of Mycobacterium tuberculosis depends on lipoamide dehydrogenase, a member of three multienzyme complexes. Cell Host Microbe 9 (2011), 21–31.
32. 32 Wagner, T., et al. A dual conformation of the post-decarboxylation intermediate is associated with distinct enzyme states in mycobacterial KGD (α-ketoglutarate decarboxylase). Biochem. J. 457 (2014), 425–434.
33. 33 Maksymiuk, C., et al. E1 of α-ketoglutarate dehydrogenase defends Mycobacterium tuberculosis against glutamate anaplerosis and nitroxidative stress. Proc. Natl. Acad. Sci. U. S. A. 112 (2015), E5834–E5843.
34. 34 Marrero, J., et al. Gluconeogenic carbon flow of tricarboxylic acid cycle intermediates is critical for Mycobacterium tuberculosis to establish and maintain infection. Proc. Natl. Acad. Sci. U. S. A. 107 (2010), 9819–9824.
35. 35 Liu, K., et al. pckA-deficient Mycobacterium bovis BCG shows attenuated virulence in mice and in macrophages. Microbiol. Read. Engl. 149 (2003), 1829–1835.
36. 36 Ganapathy, U., et al. Two enzymes with redundant fructose bisphosphatase activity sustain gluconeogenesis and virulence in Mycobacterium tuberculosis. Nat. Commun., 6, 2015, 7912.
37. 37 Gutka, H.J., et al. glpx Gene in Mycobacterium tuberculosis is required for in vitro gluconeogenic growth and in vivo survival. PLoS One, 10, 2015, e0138436.
38. 38 Watanabe, S., et al. Fumarate reductase activity maintains an energized membrane in anaerobic Mycobacterium tuberculosis. PLoS Pathog., 7, 2011, e1002287.
39. 39 Eoh, H., Rhee, K.Y., Multifunctional essentiality of succinate metabolism in adaptation to hypoxia in Mycobacterium tuberculosis. Proc. Natl. Acad. Sci. U. S. A. 110 (2013), 6554–6559.
40. 40 Chen, L., Vitkup, D., Distribution of orphan metabolic activities. Trends Biotechnol. 25 (2007), 343–348.
41. 41 Prosser, G.A., et al. Metabolomic strategies for the identification of new enzyme functions and metabolic pathways. EMBO Rep. 15 (2014), 657–669.
42. 42 de Carvalho, L.P.S., Activity-based metabolomic profiling of enzymatic function: identification of Rv1248c as a mycobacterial 2-hydroxy-3-oxoadipate synthase. Chem. Biol. 17 (2010), 323–332.
43. 43 Larrouy-Maumus, G., Discovery of a glycerol 3-phosphate phosphatase reveals glycerophospholipid polar head recycling in Mycobacterium tuberculosis. Proc. Natl. Acad. Sci. U. S. A. 110 (2013), 11320–11325.
44. 44 Sévin, D.C., et al. Nontargeted in vitro metabolomics for high-throughput identification of novel enzymes in Escherichia coli. Nat. Methods, 2016, 10.1038/nmeth.4103 Published online December 12, 2016.
45. 45 Meissner-Roloff, R.J., A metabolomics investigation of a hyper- and hypo-virulent phenotype of Beijing lineage M tuberculosis. Metabolomics 8 (2012), 1194–1203.
46. 46 Layre, E., et al. Molecular profiling of Mycobacterium tuberculosis identifies tuberculosinyl nucleoside products of the virulence-associated enzyme Rv3378c. Proc. Natl. Acad. Sci. U. S. A. 111 (2014), 2978–2983.
47. 47 Lau, S.K.P., et al. Identification of specific metabolites in culture supernatant of Mycobacterium tuberculosis using metabolomics: exploration of potential biomarkers. Emerg. Microbes Infect., 4, 2015, e6.
48. 48 Kana, B.D., et al. Future target-based drug discovery for tuberculosis?. Tuberculosis 94 (2014), 551–556.
49. 49 Mikušová, K., Ekins, S., Learning from the past for TB drug discovery in the future. Drug Discov. Today, 2016, 10.1016/j.drudis.2016.09.025 Published online October 4, 2016.
50. 50 Pethe, K., et al. A chemical genetic screen in Mycobacterium tuberculosis identifies carbon-source-dependent growth inhibitors devoid of in vivo efficacy. Nat. Commun., 1, 2010, 57.
51. 51 Bryk, R., et al. Triazaspirodimethoxybenzoyls as selective inhibitors of mycobacterial lipoamide dehydrogenase. Biochemistry (Mosc.) 49 (2010), 1616–1627.
52. 52 Schnappinger, D., Genetic approaches to facilitate antibacterial drug development. Cold Spring Harb. Perspect. Med., 5, 2015, a021139.
53. 53 Albesa-Jové, D., et al. Rv2466c Mediates the activation of TP053 To kill replicating and non-replicating Mycobacterium tuberculosis. ACS Chem. Biol. 9 (2014), 1567–1575.
54. 54 Ioerger, T.R., et al. Identification of new drug targets and resistance mechanisms in Mycobacterium tuberculosis. PLoS One, 8, 2013, e75245.
55. 55 Warrier, T., et al. N-methylation of a bactericidal compound as a resistance mechanism in Mycobacterium tuberculosis. Proc. Natl. Acad. Sci. U. S. A., 2016, E4523–E4530.
56. 56 Prosser, G.A., et al. Glutamate racemase is the primary target of β-chloro-D-alanine in Mycobacterium tuberculosis. Antimicrob. Agents Chemother. 60 (2016), 6091–6099.
57. 57 Halouska, S., et al. Use of NMR metabolomics to analyze the targets of D-cycloserine in mycobacteria: role of D-alanine racemase. J. Proteome Res. 6 (2007), 4608–4614.
58. 58 Halouska, S., et al. Metabolomics analysis identifies d-alanine-d-alanine ligase as the primary lethal target of d-cycloserine in mycobacteria. J. Proteome Res. 13 (2014), 1065–1076.
59. 59 Prosser, G.A., de Carvalho, L.P.S., Metabolomics reveal d-alanine:d-alanine ligase as the target of D-cycloserine in Mycobacterium tuberculosis. ACS Med. Chem. Lett. 4 (2013), 1233–1237.
60. 60 Boshoff, H.I.M., et al. The transcriptional responses of Mycobacterium tuberculosis to inhibitors of metabolism: novel insights into drug mechanisms of action. J. Biol. Chem. 279 (2004), 40174–40184.
61. 61 Brazas, M.D., Hancock, R.E.W., Using microarray gene signatures to elucidate mechanisms of antibiotic action and resistance. Drug Discov. Today 10 (2005), 1245–1252.
62. 62 Hutter, B., et al. Prediction of mechanisms of action of antibacterial compounds by gene expression profiling. Antimicrob. Agents Chemother. 48 (2004), 2838–2844.
63. 63 Hughes, T.R., et al. Functional discovery via a compendium of expression profiles. Cell 102 (2000), 109–126.
64. 64 Halouska, S., et al. Predicting the in vivo mechanism of action for drug leads using NMR metabolomics. ACS Chem. Biol. 7 (2012), 166–171.
65. 65 Zhang, Y., The magic bullets and tuberculosis drug targets. Annu. Rev. Pharmacol. Toxicol. 45 (2005), 529–564.
66. 66 Chakraborty, S., et al. Para-aminosalicylic acid acts as an alternative substrate of folate metabolism in Mycobacterium tuberculosis. Science 339 (2013), 88–91.
67. 67 Mori, G., et al. Thiophenecarboxamide derivatives activated by EthA kill Mycobacterium tuberculosis by inhibiting the CTP synthetase PyrG. Chem. Biol. 22 (2015), 917–927.
68. 68 Nguyen, L., Thompson, C.J., Foundations of antibiotic resistance in bacterial physiology: the mycobacterial paradigm. Trends Microbiol. 14 (2006), 304–312.
69. 69 Nandakumar, M., et al. Isocitrate lyase mediates broad antibiotic tolerance in Mycobacterium tuberculosis. Nat. Commun., 5, 2014, 4306.
70. 70 du Preez, I., Loots, D.T., Altered fatty acid metabolism due to rifampicin-resistance conferring mutations in the rpoB Gene of Mycobacterium tuberculosis: mapping the potential of pharmaco-metabolomics for global health and personalized medicine. Omics J. Integr. Biol. 16 (2012), 596–603.
71. 71 Loots, D.T., New insights into the survival mechanisms of rifampicin-resistant Mycobacterium tuberculosis. J. Antimicrob. Chemother. 71 (2016), 655–660.
72. 72 Lahiri, N., et al. Rifampin resistance mutations are associated with broad chemical remodeling of Mycobacterium tuberculosis. J. Biol. Chem. 291 (2016), 14248–14256.
73. 73 Loots, D.T., An altered Mycobacterium tuberculosis metabolome induced by katG mutations resulting in isoniazid resistance. Antimicrob. Agents Chemother. 58 (2014), 2144–2149.
74. 74 Carroll, P., et al. Identifying vulnerable pathways in Mycobacterium tuberculosis by using a knockdown approach. Appl. Environ. Microbiol. 77 (2011), 5040–5043.
75. 75 Puckett, S., et al. Inactivation of fructose-1,6-bisphosphate aldolase prevents optimal co-catabolism of glycolytic and gluconeogenic carbon substrates in Mycobacterium tuberculosis. PLoS Pathog., 10, 2014, e1004144.
76. 76 Wei, J.-R., et al. Depletion of antibiotic targets has widely varying effects on growth. Proc. Natl. Acad. Sci. U. S. A. 108 (2011), 4176–4181.
77. 77 Park, S.W., et al. Evaluating the sensitivity of Mycobacterium tuberculosis to biotin deprivation using regulated gene expression. PLoS Pathog., 7, 2011, e1002264.
78. 78 Evans, J.C., et al. Validation of CoaBC as a bactericidal target in the coenzyme A pathway of Mycobacterium tuberculosis. ACS Infect. Dis. 2 (2016), 958–968.
79. 79 Evans, J.C., Mizrahi, V., The application of tetracycline regulated gene expression systems in the validation of novel drug targets in Mycobacterium tuberculosis. Front. Microbiol., 6, 2015, 812.
80. 80 National Institutes of Health Office of Strategic Coordination – The Common Fund. Metabolomics. Updated January 6, 2017. https://commonfund.nih.gov/metabolomics.