Whole Cell Target Engagement Identifies Novel Inhibitors of Mycobacterium tuberculosis Decaprenylphosphoryl-β- d -ribose Oxidase

ACS Infectious Diseases

Volumn 1, Issue 12, 2016, Pages 615-626

  Batt, Sarah M ^a   Cacho Izquierdo, Monica ^b   Castro Pichel, Julia ^b   Stubbs, Christopher J ^d   Vela Glez Del Peral, Laura ^c   Pérez Herrán, Esther ^b   Dhar, Neeraj ^f   Mouzon, Bernadette ^d   Rees, Mike ^d   Hutchinson, Jonathan P ^d   Young, Robert J ^e   McKinney, John D ^f   Barros Aguirre, David ^b   Ballell, Lluis ^b   Besra, Gurdyal S ^a   Argyrou, Argyrides ^d  

^a UNIVERSITY OF BIRMINGHAM   (United Kingdom)

^b Diseases of the Developing World   (Spain)

^c GLAXOSMITHKLINE   (Spain)

^d Department of Biological Sciences ^*  (United Kingdom)

^e GLAXOSMITHKLINE   (United Kingdom)

^f EPFL   (Switzerland)

Author keywords

drug discovery; multicopy suppression; target overexpression; time lapse microscopy

Indexed keywords

ANTIMYCOBACTERIAL AGENT; BTZ 043; DECAPRENYLPHOSPHORYL BETA DEXTRO RIBOSE OXIDASE; GSK 018; GSK 058; GSK 059; GSK 074; GSK 155; GSK 303; GSK 305; GSK 310; GSK 710; GSK 717; GSK 763; GSK 944; OXIDOREDUCTASE; TCA1; UNCLASSIFIED DRUG;

ARTICLE; BACTERIAL GROWTH; BACTERIUM MUTANT; BINDING AFFINITY; CYTOLYSIS; ENZYME INHIBITION; MINIMUM INHIBITORY CONCENTRATION; MYCOBACTERIUM TUBERCULOSIS; NONHUMAN; POINT MUTATION; PRIORITY JOURNAL; TARGET CELL;

EID: 84969242634     PISSN: None     EISSN: 23738227     Source Type: Journal    
DOI: 10.1021/acsinfecdis.5b00065     Document Type: Article

References (40)

1. Gler, M. T., Skripconoka, V., Sanchez-Garavito, E., Xiao, H., Cabrera-Rivero, J. L., Vargas-Vasquez, D. E., Gao, M., Awad, M., Park, S. K., Shim, T. S., Suh, G. Y., Danilovits, M., Ogata, H., Kurve, A., Chang, J., Suzuki, K., Tupasi, T., Koh, W. J., Seaworth, B., Geiter, L. J., and Wells, C. D. (2012) Delamanid for multidrug-resistant pulmonary tuberculosis N. Engl. J. Med. 366, 2151-2160 10.1056/NEJMoa1112433
2. Zumla, A., Nahid, P., and Cole, S. T. (2013) Advances in the development of new tuberculosis drugs and treatment regimens Nat. Rev. Drug Discovery 12, 388-404 10.1038/nrd4001
3. Wright, A., Zignol, M., Van Deun, A., Falzon, D., Gerdes, S. R., Feldman, K., Hoffner, S., Drobniewski, F., Barrera, L., van Soolingen, D., Boulabhal, F., Paramasivan, C. N., Kam, K. M., Mitarai, S., Nunn, P., and Raviglione, M. (2009) Epidemiology of antituberculosis drug resistance 2002-07: an updated analysis of the global project on anti-tuberculosis drug resistance surveillance Lancet 373, 1861-1873 10.1016/S0140-6736(09)60331-7
4. Ballell, L., Bates, R. H., Young, R. J., Alvarez-Gomez, D., Alvarez-Ruiz, E., Barroso, V., Blanco, D., Crespo, B., Escribano, J., Gonzalez, R., Lozano, S., Huss, S., Santos-Villarejo, A., Martin-Plaza, J. J., Mendoza, A., Rebollo-Lopez, M. J., Remuinan-Blanco, M., Lavandera, J. L., Perez-Herran, E., Gamo-Benito, F. J., Garcia-Bustos, J. F., Barros, D., Castro, J. P., and Cammack, N. (2013) Fueling open-source drug discovery: 177 small-molecule leads against tuberculosis ChemMedChem 8, 313-321 10.1002/cmdc.201200428
5. Remuinan, M. J., Perez-Herran, E., Rullas, J., Alemparte, C., Martinez-Hoyos, M., Dow, D. J., Afari, J., Mehta, N., Esquivias, J., Jimenez, E., Ortega-Muro, F., Fraile-Gabaldon, M. T., Spivey, V. L., Loman, N. J., Pallen, M. J., Constantinidou, C., Minick, D. J., Cacho, M., Rebollo-Lopez, M. J., Gonzalez, C., Sousa, V., Angulo-Barturen, I., Mendoza-Losana, A., Barros, D., Besra, G. S., Ballell, L., and Cammack, N. (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 10.1371/journal.pone.0060933
6. Abrahams, K. A., Cox, J. A., Spivey, V. L., Loman, N. J., Pallen, M. J., Constantinidou, C., Fernandez, R., Alemparte, C., Remuinan, M. J., Barros, D., Ballell, L., and Besra, G. S. (2012) Identification of novel imidazo[1,2-a]pyridine inhibitors targeting M. tuberculosis QcrB PLoS One 7, e52951 10.1371/journal.pone.0052951
7. Encinas, L., O'Keefe, H., Neu, M., Remuinan, M. J., Patel, A. M., Guardia, A., Davie, C. P., Perez-Macias, N., Yang, H., Convery, M. A., Messer, J. A., Perez-Herran, E., Centrella, P. A., Alvarez-Gomez, D., Clark, M. A., Huss, S., O'Donovan, G. K., Ortega-Muro, F., McDowell, W., Castaneda, P., Arico-Muendel, C. C., Pajk, S., Rullas, J., Angulo-Barturen, I., Alvarez-Ruiz, E., Mendoza-Losana, A., Ballell Pages, L., Castro-Pichel, J., and Evindar, G. (2014) Encoded library technology as a source of hits for the discovery and lead optimization of a potent and selective class of bactericidal direct inhibitors of Mycobacterium tuberculosis InhA J. Med. Chem. 57, 1276-1288 10.1021/jm401326j
8. Knapp, S., Arruda, P., Blagg, J., Burley, S., Drewry, D. H., Edwards, A., Fabbro, D., Gillespie, P., Gray, N. S., Kuster, B., Lackey, K. E., Mazzafera, P., Tomkinson, N. C., Willson, T. M., Workman, P., and Zuercher, W. J. (2013) A public-private partnership to unlock the untargeted kinome Nat. Chem. Biol. 9, 3-6 10.1038/nchembio.1113
9. Mikusova, K., Huang, H., Yagi, T., Holsters, M., Vereecke, D., D'Haeze, W., Scherman, M. S., Brennan, P. J., McNeil, M. R., and Crick, D. C. (2005) Decaprenylphosphoryl arabinofuranose, the donor of the d -arabinofuranosyl residues of mycobacterial arabinan, is formed via a two-step epimerization of decaprenylphosphoryl ribose J. Bacteriol. 187, 8020-8025 10.1128/JB.187.23.8020-8025.2005
10. Wolucka, B. A., McNeil, M. R., de Hoffmann, E., Chojnacki, T., and Brennan, P. J. (1994) Recognition of the lipid intermediate for arabinogalactan/arabinomannan biosynthesis and its relation to the mode of action of ethambutol on mycobacteria J. Biol. Chem. 269, 23328-23335
11. Alderwick, L. J., Radmacher, E., Seidel, M., Gande, R., Hitchen, P. G., Morris, H. R., Dell, A., Sahm, H., Eggeling, L., and Besra, G. S. (2005) Deletion of Cg-emb in corynebacterianeae leads to a novel truncated cell wall arabinogalactan, whereas inactivation of Cg-ubiA results in an arabinan-deficient mutant with a cell wall galactan core J. Biol. Chem. 280, 32362-32371 10.1074/jbc.M506339200
12. Kolly, G. S., Boldrin, F., Sala, C., Dhar, N., Hartkoorn, R. C., Ventura, M., Serafini, A., McKinney, J. D., Manganelli, R., and Cole, S. T. (2014) Assessing the essentiality of the decaprenyl-phospho- d -arabinofuranose pathway in Mycobacterium tuberculosis using conditional mutants Mol. Microbiol. 92, 194-211 10.1111/mmi.12546
13. Brecik, M., Centarova, I., Mukherjee, R., Kolly, G. S., Huszar, S., Bobovska, A., Kilacskova, E., Mokosova, V., Svetlikova, Z., Sarkan, M., Neres, J., Kordulakova, J., Cole, S. T., and Mikusova, K. (2015) DprE1 is a vulnerable tuberculosis drug target due to its cell wall localization ACS Chem. Biol. 10, 1631-1636 10.1021/acschembio.5b00237
14. Makarov, V., Manina, G., Mikusova, K., Mollmann, U., Ryabova, O., Saint-Joanis, B., Dhar, N., Pasca, M. R., Buroni, S., Lucarelli, A. P., Milano, A., De, R. E., Belanova, M., Bobovska, A., Dianiskova, P., Kordulakova, J., Sala, C., Fullam, E., Schneider, P., McKinney, J. D., Brodin, P., Christophe, T., Waddell, S., Butcher, P., Albrethsen, J., Rosenkrands, I., Brosch, R., Nandi, V., Bharath, S., Gaonkar, S., Shandil, R. K., Balasubramanian, V., Balganesh, T., Tyagi, S., Grosset, J., Riccardi, G., and Cole, S. T. (2009) Benzothiazinones kill Mycobacterium tuberculosis by blocking arabinan synthesis Science 324, 801-804 10.1126/science.1171583
15. Batt, S. M., Jabeen, T., Bhowruth, V., Quill, L., Lund, P. A., Eggeling, L., Alderwick, L. J., Futterer, K., and Besra, G. S. (2012) Structural basis of inhibition of Mycobacterium tuberculosis DprE1 by benzothiazinone inhibitors Proc. Natl. Acad. Sci. U. S. A. 109, 11354-11359 10.1073/pnas.1205735109
16. Chatterji, M., Shandil, R., Manjunatha, M. R., Solapure, S., Ramachandran, V., Kumar, N., Saralaya, R., Panduga, V., Reddy, J., Kr, P., Sharma, S., Sadler, C., Cooper, C. B., Mdluli, K., Iyer, P. S., Narayanan, S., and Shirude, P. S. (2014) 1,4-Azaindole, a potential drug candidate for treatment of tuberculosis Antimicrob. Agents Chemother. 58, 5325-5331 10.1128/AAC.03233-14
17. Naik, M., Humnabadkar, V., Tantry, S. J., Panda, M., Narayan, A., Guptha, S., Panduga, V., Manjrekar, P., Jena, L. K., Koushik, K., Shanbhag, G., Jatheendranath, S., Manjunatha, M. R., Gorai, G., Bathula, C., Rudrapatna, S., Achar, V., Sharma, S., Ambady, A., Hegde, N., Mahadevaswamy, J., Kaur, P., Sambandamurthy, V. K., Awasthy, D., Narayan, C., Ravishankar, S., Madhavapeddi, P., Reddy, J., Prabhakar, K., Saralaya, R., Chatterji, M., Whiteaker, J., McLaughlin, B., Chiarelli, L. R., Riccardi, G., Pasca, M. R., Binda, C., Neres, J., Dhar, N., Signorino-Gelo, F., McKinney, J. D., Ramachandran, V., Shandil, R., Tommasi, R., Iyer, P. S., Narayanan, S., Hosagrahara, V., Kavanagh, S., Dinesh, N., and Ghorpade, S. R. (2014) 4-Aminoquinolone piperidine amides: noncovalent inhibitors of DprE1 with long residence time and potent antimycobacterial activity J. Med. Chem. 57, 5419-5434 10.1021/jm5005978
18. Panda, M., Ramachandran, S., Ramachandran, V., Shirude, P. S., Humnabadkar, V., Nagalapur, K., Sharma, S., Kaur, P., Guptha, S., Narayan, A., Mahadevaswamy, J., Ambady, A., Hegde, N., Rudrapatna, S. S., Hosagrahara, V. P., Sambandamurthy, V. K., and Raichurkar, A. (2014) Discovery of pyrazolopyridones as a novel class of noncovalent DprE1 inhibitor with potent anti-mycobacterial activity J. Med. Chem. 57, 4761-4771 10.1021/jm5002937
19. Shirude, P. S., Shandil, R. K., Manjunatha, M. R., Sadler, C., Panda, M., Panduga, V., Reddy, J., Saralaya, R., Nanduri, R., Ambady, A., Ravishankar, S., Sambandamurthy, V. K., Humnabadkar, V., Jena, L. K., Suresh, R. S., Srivastava, A., Prabhakar, K. R., Whiteaker, J., McLaughlin, R. E., Sharma, S., Cooper, C. B., Mdluli, K., Butler, S., Iyer, P. S., Narayanan, S., and Chatterji, M. (2014) Lead optimization of 1,4-azaindoles as antimycobacterial agents J. Med. Chem. 57, 5728-5737 10.1021/jm500571f
20. Shirude, P. S., Shandil, R., Sadler, C., Naik, M., Hosagrahara, V., Hameed, S., Shinde, V., Bathula, C., Humnabadkar, V., Kumar, N., Reddy, J., Panduga, V., Sharma, S., Ambady, A., Hegde, N., Whiteaker, J., McLaughlin, R. E., Gardner, H., Madhavapeddi, P., Ramachandran, V., Kaur, P., Narayan, A., Guptha, S., Awasthy, D., Narayan, C., Mahadevaswamy, J., Vishwas, K. G., Ahuja, V., Srivastava, A., Prabhakar, K. R., Bharath, S., Kale, R., Ramaiah, M., Choudhury, N. R., Sambandamurthy, V. K., Solapure, S., Iyer, P. S., Narayanan, S., and Chatterji, M. (2013) Azaindoles: noncovalent DprE1 inhibitors from scaffold morphing efforts, kill Mycobacterium tuberculosis and are efficacious in vivo J. Med. Chem. 56, 9701-9708 10.1021/jm401382v
21. Wang, F., Sambandan, D., Halder, R., Wang, J., Batt, S. M., Weinrick, B., Ahmad, I., Yang, P., Zhang, Y., Kim, J., Hassani, M., Huszar, S., Trefzer, C., Ma, Z., Kaneko, T., Mdluli, K. E., Franzblau, S., Chatterjee, A. K., Johnsson, K., Mikusova, K., Besra, G. S., Futterer, K., Robbins, S. H., Barnes, S. W., Walker, J. R., Jacobs, W. R., Jr., and Schultz, P. G. (2013) Identification of a small molecule with activity against drug-resistant and persistent tuberculosis Proc. Natl. Acad. Sci. U. S. A. 110, E2510-E2517 10.1073/pnas.1309171110
22. Neres, J., Hartkoorn, R. C., Chiarelli, L. R., Gadupudi, R., Pasca, M. R., Mori, G., Venturelli, A., Savina, S., Makarov, V., Kolly, G. S., Molteni, E., Binda, C., Dhar, N., Ferrari, S., Brodin, P., Delorme, V., Landry, V., de Jesus Lopes Ribeiro, A. L., Farina, D., Saxena, P., Pojer, F., Carta, A., Luciani, R., Porta, A., Zanoni, G., De, R. E., Costi, M. P., Riccardi, G., and Cole, S. T. (2015) 2-Carboxyquinoxalines kill Mycobacterium tuberculosis through noncovalent inhibition of DprE1 ACS Chem. Biol. 10, 705-714 10.1021/cb5007163
23. Goldman, R. C. (2013) Why are membrane targets discovered by phenotypic screens and genome sequencing in Mycobacterium tuberculosis? Tuberculosis 93, 569-588 10.1016/j.tube.2013.09.003
24. Li, X., Zolli-Juran, M., Cechetto, J. D., Daigle, D. M., Wright, G. D., and Brown, E. D. (2004) Multicopy suppressors for novel antibacterial compounds reveal targets and drug efflux susceptibility Chem. Biol. 11, 1423-1430 10.1016/j.chembiol.2004.08.014
25. Luesch, H., Wu, T. Y., Ren, P., Gray, N. S., Schultz, P. G., and Supek, F. (2005) A genome-wide overexpression screen in yeast for small-molecule target identification Chem. Biol. 12, 55-63 10.1016/j.chembiol.2004.10.015
26. Stover, C. K., de la Cruz, V. F., Fuerst, T. R., Burlein, J. E., Benson, L. A., Bennett, L. T., Bansal, G. P., Young, J. F., Lee, M. H., and Hatfull, G. F. (1991) New use of BCG for recombinant vaccines Nature 351, 456-460 10.1038/351456a0
27. Franzblau, S. G., Witzig, R. S., McLaughlin, J. C., Torres, P., Madico, G., Hernandez, A., Degnan, M. T., Cook, M. B., Quenzer, V. K., Ferguson, R. M., and Gilman, R. H. (1998) Rapid, low-technology MIC determination with clinical Mycobacterium tuberculosis isolates by using the microplate alamar blue assay J. Clin. Microbiol. 36, 362-366
28. Neres, J., Pojer, F., Molteni, E., Chiarelli, L. R., Dhar, N., Boy-Rottger, S., Buroni, S., Fullam, E., Degiacomi, G., Lucarelli, A. P., Read, R. J., Zanoni, G., Edmondson, D. E., De, R. E., Pasca, M. R., McKinney, J. D., Dyson, P. J., Riccardi, G., Mattevi, A., Cole, S. T., and Binda, C. (2012) Structural basis for benzothiazinone-mediated killing of Mycobacterium tuberculosis Sci. Transl. Med. 4, 150ra121 10.1126/scitranslmed.3004395
29. Wakamoto, Y., Dhar, N., Chait, R., Schneider, K., Signorino-Gelo, F., Leibler, S., and McKinney, J. D. (2013) Dynamic persistence of antibiotic-stressed mycobacteria Science 339, 91-95 10.1126/science.1229858
30. Guo, H., Seet, Q., Denkin, S., Parsons, L., and Zhang, Y. (2006) Molecular characterization of isoniazid-resistant clinical isolates of Mycobacterium tuberculosis from the USA J. Med. Microbiol. 55, 1527-1531 10.1099/jmm.0.46718-0
31. Hiramatsu, K. (2001) Vancomycin-resistant Staphylococcus aureus: a new model of antibiotic resistance Lancet Infect. Dis. 1, 147-155 10.1016/S1473-3099(01)00091-3
32. Flensburg, J. and Skold, O. (1987) Massive overproduction of dihydrofolate reductase in bacteria as a response to the use of trimethoprim Eur. J. Biochem. 162, 473-476 10.1111/j.1432-1033.1987.tb10664.x
33. Banerjee, A., Dubnau, E., Quemard, A., Balasubramanian, V., Um, K. S., Wilson, T., Collins, D., de, L. G., and Jacobs, W. R., Jr. (1994) InhA, a gene encoding a target for isoniazid and ethionamide in Mycobacterium tuberculosis Science 263, 227-230 10.1126/science.8284673
34. Shi, W., Zhang, X., Jiang, X., Yuan, H., Lee, J. S., Barry, C. E., III, Wang, H., Zhang, W., and Zhang, Y. (2011) Pyrazinamide inhibits trans-translation in Mycobacterium tuberculosis Science 333, 1630-1632 10.1126/science.1208813
35. Bunnage, M. E., Chekler, E. L., and Jones, L. H. (2013) Target validation using chemical probes Nat. Chem. Biol. 9, 195-199 10.1038/nchembio.1197
36. Simon, G. M., Niphakis, M. J., and Cravatt, B. F. (2013) Determining target engagement in living systems Nat. Chem. Biol. 9, 200-205 10.1038/nchembio.1211
37. Depardieu, F., Podglajen, I., Leclercq, R., Collatz, E., and Courvalin, P. (2007) Modes and modulations of antibiotic resistance gene expression Clin. Microbiol. Rev. 20, 79-114 10.1128/CMR.00015-06
38. Copeland, R. A. (2005) Tight binding inhibition. In Evaluation of Enzyme Inhibitors in Drug Discovery: A Guide for Medicinal Chemists and Pharmacologists, pp 178-213, Wiley, Hoboken, NJ, USA.
39. Harbury, H. A., Lanoue, K. F., Loach, P. A., and Amick, R. M. (1959) Molecular interaction of isoalloxazine derivatives. II Proc. Natl. Acad. Sci. U. S. A. 45, 1708-1717 10.1073/pnas.45.12.1708
40. Taneja, N. K. and Tyagi, J. S. (2007) Resazurin reduction assays for screening of anti-tubercular compounds against dormant and actively growing Mycobacterium tuberculosis, Mycobacterium bovis BCG and Mycobacterium smegmatis J. Antimicrob. Chemother. 60, 288-293 10.1093/jac/dkm207