Cryptosporidium and toxoplasma parasites are inhibited by a benzoxaborole targeting leucyl-tRNA synthetase

Antimicrobial Agents and Chemotherapy

Volumn 60, Issue 10, 2016, Pages 5817-5827

  Palencia, Andrés ^a,b   Liu, Ru Juan ^c   Lukarska, Maria ^a   Gut, Jiri ^d   Bougdour, Alexandre ^b   Touquet, Bastien ^b   Wang, En Duo ^c   Li, Xianfeng ^e   Alley, M R K ^e   Freund, Yvonne R ^e   Rosenthal, Philip J ^d   Hakimi, Mohamed Ali ^b   Cusack, Stephen ^a  

^a EUROPEAN MOLECULAR BIOLOGY LABORATORY   (France)

^b UNIV GRENOBLE ALPES   (France)

^c INSTITUTE OF BIOCHEMISTRY AND CELL BIOLOGY   (China)

^d UNIVERSITY OF CALIFORNIA   (United States)

^e PFIZER INC   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

3 (AMINOMETHYL) 4 BROMO 7 ETHOXYBENZO[C][1,2]OXABOROL 1(3H)OL; 3 (AMINOMETHYL) 4 CHLORO 7 ETHOXYBENZO[C][1,2]OXABOROL 1(3H)OL; ANTIPARASITIC AGENT; ANTISPOROZOAL AGENT; BORON DERIVATIVE; LEUCINE TRANSFER RNA LIGASE; NITAZOXANIDE; NORVALINE; TRANSFER RNA; UNCLASSIFIED DRUG; AN6426; ANTIPROTOZOAL AGENT; ENZYME INHIBITOR;

ANIMAL CELL; ANTIPROTOZOAL ACTIVITY; ARTICLE; BINDING AFFINITY; CONTROLLED STUDY; COVALENT BOND; CRYPTOSPORIDIUM MURIS; CRYPTOSPORIDIUM PARVUM; CRYSTAL STRUCTURE; DRUG EFFICACY; DRUG IDENTIFICATION; DRUG MECHANISM; DRUG TARGETING; EC50; HUMAN; HUMAN CELL; MAMMAL CELL; NONHUMAN; PRIORITY JOURNAL; PROTEIN SYNTHESIS; RNA EDITING; STRUCTURE ACTIVITY RELATION; TOXOPLASMA GONDII; ANIMAL; ANTAGONISTS AND INHIBITORS; CHEMISTRY; DOG; DRUG EFFECTS; FIBROBLAST; MDCK CELL LINE; METABOLISM; MOLECULAR DOCKING; PARASITOLOGY; PRECLINICAL STUDY; PROCEDURES; PROTEIN CONFORMATION; TOXOPLASMA; X RAY CRYSTALLOGRAPHY;

ANIMALS; ANTIPROTOZOAL AGENTS; BORON COMPOUNDS; CRYPTOSPORIDIUM PARVUM; CRYSTALLOGRAPHY, X-RAY; DOGS; DRUG EVALUATION, PRECLINICAL; ENZYME INHIBITORS; FIBROBLASTS; HUMANS; LEUCINE-TRNA LIGASE; MADIN DARBY CANINE KIDNEY CELLS; MOLECULAR DOCKING SIMULATION; PROTEIN CONFORMATION; TOXOPLASMA;

EID: 84992731507     PISSN: 00664804     EISSN: 10986596     Source Type: Journal    
DOI: 10.1128/AAC.00873-16     Document Type: Article

References (66)

1. Checkley W, White AC, Jaganath D, Arrowood MJ, Chalmers RM, Chen X-M, Fayer R, Griffiths JK, Guerrant RL, Hedstrom L, Huston CD, Kotloff KL, Kang G, Mead JR, Miller M, Petri WA, Priest JW, Roos DS, Striepen B, Thompson RCA, Ward HD, Van Voorhis WA, Xiao L, Zhu G, Houpt ER. 2015. A review of the global burden, novel diagnostics, therapeutics, and vaccine targets for cryptosporidium. Lancet Infect Dis 15:85-94. http://dx.doi.org/10.1016/S1473-3099(14)70772-8.
2. Kotloff KL, Nataro JP, Blackwelder WC, Nasrin D, Farag TH, Panchalingam S, Wu Y, Sow SO, Sur D, Breiman RF, Faruque AS, Zaidi AK, Saha D, Alonso PL, Tamboura B, Sanogo D, Onwuchekwa U, Manna B, Ramamurthy T, Kanungo S, Ochieng JB, Omore R, Oundo JO, Hossain A, Das SK, Ahmed S, Qureshi S, Quadri F, Adegbola RA, Antonio M, Hossain MJ, Akinsola A, Mandomando I, Nhampossa T, Acácio S, Biswas K, O'Reilly CE, Mintz ED, Berkeley LY, Muhsen K, Sommerfelt H, Robins-Browne RM, Levine MM. 2013. Burden and aetiology of diarrhoeal disease in infants and young children in developing countries (the Global Enteric Multicenter Study, GEMS): a prospective, case-control study. Lancet 382:209-222. http://dx.doi.org/10.1016/S0140-6736(13)60844-2.
3. Rossignol J-F. 2010. Cryptosporidium and Giardia: treatment options and prospects for new drugs. Exp Parasitol 124:45-53. http://dx.doi.org/10.1016/j.exppara.2009.07.005.
4. Striepen B. 2013. Parasitic infections: time to tackle cryptosporidiosis. Nature 503:189-191. http://dx.doi.org/10.1038/503189a.
5. MacKenzie WR, Hoxie NJ, Proctor ME, Gradus MS, Blair KA, Peterson DE, Kazmierczak JJ, Addiss DG, Fox KR, Rose JB. 1994. A massive outbreak in Milwaukee of Cryptosporidium infection transmitted through the public water supply.NEngl J Med 331:161-167. http://dx.doi.org/10.1056/NEJM199407213310304.
6. Amadi B, Mwiya M, Musuku J, Watuka A, Sianongo S, Ayoub A, Kelly P. 2002. Effect of nitazoxanide on morbidity and mortality in Zambian children with cryptosporidiosis: a randomised controlled trial. Lancet 360:1375-1380. http://dx.doi.org/10.1016/S0140-6736(02)11401-2.
7. Pappas G, Roussos N, Falagas ME. 2009. Toxoplasmosis snapshots: global status of Toxoplasma gondii seroprevalence and implications for pregnancy and congenital toxoplasmosis. Int J Parasitol 39:1385-1394. http://dx.doi.org/10.1016/j.ijpara.2009.04.003.
8. Flegr J, Prandota J, Sovičková M, Israili ZH. 2014. Toxoplasmosis-a global threat. Correlation of latent toxoplasmosis with specific disease burden in a set of 88 countries. PLoS One 9:e90203. http://dx.doi.org/10 .1371/journal.pone.0090203.
9. Luft BJ, Remington JS. 1992. Toxoplasmic encephalitis in AIDS. Clin Infect Dis 15:211-222. http://dx.doi.org/10.1093/clinids/15.2.211.
10. Montoya JG, Liesenfeld O. 2004. Toxoplasmosis. Lancet 363:1965-1976. http://dx.doi.org/10.1016/S0140-6736(04)16412-X.
11. Dannemann B, McCutchan JA, Israelski D, Antoniskis D, Leport C, Luft B, Nussbaum J, Clumeck N, Morlat P, Chiu J. 1992. Treatment of toxoplasmic encephalitis in patients with AIDS. A randomized trial comparing pyrimethamine plus clindamycin to pyrimethamine plus sulfadiazine. The California Collaborative Treatment Group. Ann Intern Med 116:33-43.
12. Farthing C, Rendel M, Currie B, Seidlin M. 1992. Azithromycin for cerebral toxoplasmosis. Lancet 339:437-438.
13. Jones JL, Parise ME, Fiore AE. 2014. Neglected parasitic infections in the United States: toxoplasmosis. Am J Trop Med Hyg 90:794-799. http://dx.doi.org/10.4269/ajtmh.13-0722.
14. Andrews KT, Fisher G, Skinner-Adams TS. 2014. Drug repurposing and human parasitic protozoan diseases. Int J Parasitol Drugs Drug Resist 4:95-111. http://dx.doi.org/10.1016/j.ijpddr.2014.02.002.
15. Hernandez V, Crépin T, Palencia A, Cusack S, Akama T, Baker SJ, Bu W, Feng L, Freund YR, Liu L, Meewan M, Mohan M, Mao W, Rock FL, Sexton H, Sheoran A, Zhang Y, Zhang Y-K, Zhou Y, Nieman JA, Anugula MR, Keramane EM, Savariraj K, Reddy DS, Sharma R, Subedi R, Singh R, O'Leary A, Simon NL, De Marsh PL, Mushtaq S, Warner M, Livermore DM, Alley MRK, Plattner JJ. 2013. Discovery of a novel class of boron-based antibacterials with activity against gram-negative bacteria. Antimicrob Agents Chemother 57:1394-1403. http://dx.doi.org/10.1128/AAC.02058-12.
16. Rock FL, Mao W, Yaremchuk A, Tukalo M, Crépin T, Zhou H, Zhang Y-K, Hernandez V, Akama T, Baker SJ, Plattner JJ, Shapiro L, Martinis SA, Benkovic SJ, Cusack S, Alley MRK. 2007. An antifungal agent inhibits an aminoacyl-tRNA synthetase by trapping tRNA in the editing site. Science 316:1759-1761. http://dx.doi.org/10.1126/science.1142189.
17. Ibba M, Soll D. 2000. Aminoacyl-tRNA synthesis. Annu Rev Biochem 69:617-650. http://dx.doi.org/10.1146/annurev.biochem.69.1.617.
18. Pham JS, Dawson KL, Jackson KE, Lim EE, Pasaje CFA, Turner KEC, Ralph SA. 2014. Aminoacyl-tRNA synthetases as drug targets in eukaryotic parasites. Int J Parasitol Drugs Drug Resist 4:1-13. http://dx.doi.org/10.1016/j.ijpddr.2013.10.001.
19. Schimmel P, Tao J, Hill J. 1998. Aminoacyl tRNA synthetases as targets for new anti-infectives. FASEB J 12:1599-1609.
20. Lv P-C, Zhu H-L. 2012. Aminoacyl-tRNA synthetase inhibitors as potent antibacterials. Curr Med Chem 19:3550-3563. http://dx.doi.org/10.2174/092986712801323199.
21. Vondenhoff GHM, Van Aerschot A. 2011. Aminoacyl-tRNA synthetase inhibitors as potential antibiotics. Eur J Med Chem 46:5227-5236. http://dx.doi.org/10.1016/j.ejmech.2011.08.049.
22. Elewski BE, Aly R, Baldwin SL, González Soto RF, Rich P, Weisfeld M, Wiltz H, Zane LT, Pollak R. 2015. Efficacy and safety of tavaborole topical solution, 5%, a novel boron-based antifungal agent, for the treatment of toenail onychomycosis: results from 2 randomized phase-III studies. J Am Acad Dermatol 73:62-69. http://dx.doi.org/10.1016/j.jaad .2015.04.010.
23. Sonoiki E, Palencia A, Guo D, Ahyong V, Dong C, Li X, Hernandez VS, Zhang Y-K, Choi W, Gut J, Legac J, Cooper R, Alley MRK, Freund YR, DeRisi J, Cusack S, Rosenthal PJ. 6 June 2016. Anti-malarial benzoxaboroles target P. falciparum leucyl-tRNA synthetase. Antimicrob Agents Chemother. http://dx.doi.org/10.1128/AAC.00820-16.
24. Hernandez VS, Ding C, Plattner JJ, Alley MRK, Rock F, Zhang S, Easom E, Li X, Zhou D. 2012. Benzoxaborole derivatives for treating bacterial infections. Patent WO2012033858.
25. Gut J, Nelson RG. 1999. Cryptosporidium parvum: synchronized excystation in vitro and evaluation of sporozoite infectivity with a new lectinbased assay. J Eukaryot Microbiol 46:56S-57S.
26. Kabsch W. 2010. XDS. Acta Crystallogr D Biol Crystallogr 66:125-132. http://dx.doi.org/10.1107/S0907444909047337.
27. Otwinowski Z, Minor W. 1997. Processing of X-ray diffraction data collected in oscillation mode. Methods Enzymol 276:307-326.
28. Collaborative Computational Project Number 4. 1994. The CCP4 suite: programs for protein crystallography. Acta Crystallogr D Biol Crystallogr 50:760-763. http://dx.doi.org/10.1107/S0907444994003112.
29. McCoy AJ, Grosse-Kunstleve RW, Storoni LC, Read RJ. 2005. Likelihood-enhanced fast translation functions. Acta Crystallogr D Biol Crystallogr 61:458-464. http://dx.doi.org/10.1107/S0907444905001617.
30. Emsley P, Cowtan K. 2004. Coot: model-building tools for molecular graphics. Acta Crystallogr D Biol Crystallogr 60:2126-2132. http://dx.doi.org/10.1107/S0907444904019158.
31. Murshudov GN, Vagin AA, Dodson EJ. 1997. Refinement of macromolecular structures by the maximum-likelihood method. Acta Crystallogr D Biol Crystallogr 53:240-255. http://dx.doi.org/10.1107/S0907444996012255.
32. Adams PD, Grosse-Kunstleve RW, Hung LW, Ioerger TR, McCoy AJ, Moriarty NW, Read RJ, Sacchettini JC, Sauter NK, Terwilliger TC. 2002. PHENIX: building new software for automated crystallographic structure determination. Acta Crystallogr D Biol Crystallogr 58:1948-1954. http://dx.doi.org/10.1107/S0907444902016657.
33. Arnold K, Bordoli L, Kopp J, Schwede T. 2006. The SWISS-MODEL workspace: a web-based environment for protein structure homology modelling. Bioinformatics 22:195-201. http://dx.doi.org/10.1093/bioinformatics/bti770.
34. Benkert P, Biasini M, Schwede T. 2011. Toward the estimation of the absolute quality of individual protein structure models. Bioinformatics 27:343-350. http://dx.doi.org/10.1093/bioinformatics/btq662.
35. Braun L, Cannella D, Pinheiro AM, Kieffer S, Belrhali H, Garin J, Hakimi M-A. 2009. The small ubiquitin-like modifier (SUMO)-conjugating system of Toxoplasma gondii. Int J Parasitol 39:81-90. http://dx.doi.org/10.1016/j.ijpara.2008.07.009.
36. Rossignol JF, Ayoub A, Ayers MS. 2001. Treatment of diarrhea caused by Giardia intestinalis and Entamoeba histolytica or E. dispar: a randomized, double-blind, placebo-controlled study of nitazoxanide. J Infect Dis 184: 381-384. http://dx.doi.org/10.1086/322038.
37. Palencia A, Crépin T, Vu MT, Lincecum TL, Martinis SA, Cusack S. 2012. Structural dynamics of the aminoacylation and proofreading functional cycle of bacterial leucyl-tRNA synthetase. Nat Struct Mol Biol 19: 677-684. http://dx.doi.org/10.1038/nsmb.2317.
38. Abrahamsen MS, Templeton TJ, Enomoto S, Abrahante JE, Zhu G, Lancto CA, Deng M, Liu C, Widmer G, Tzipori S, Buck GA, Xu P, Bankier AT, Dear PH, Konfortov BA, Spriggs HF, Iyer L, Anantharaman V, Aravind L, Kapur V. 2004. Complete genome sequence of the apicomplexan, Cryptosporidium parvum. Science 304:441-445. http://dx.doi.org/10.1126/science.1094786.
39. Puiu D, Enomoto S, Buck GA, Abrahamsen MS, Kissinger JC. 2004. CryptoDB: the Cryptosporidium genome resource. Nucleic Acids Res 32: D329-D331. http://dx.doi.org/10.1093/nar/gkh050.
40. Xu P, Widmer G, Wang Y, Ozaki LS, Alves JM, Serrano MG, Puiu D, Manque P, Akiyoshi D, Mackey AJ, Pearson WR, Dear PH, Bankier AT, Peterson DL, Abrahamsen MS, Kapur V, Tzipori S, Buck GA. 2004. The genome of Cryptosporidium hominis. Nature 431:1107-1112. http://dx.doi.org/10.1038/nature02977.
41. Cusack S, Yaremchuk A, Tukalo M. 2000. The 2 A crystal structure of leucyl-tRNA synthetase and its complex with a leucyl-adenylate analogue. EMBO J 19:2351-2361. http://dx.doi.org/10.1093/emboj/19.10.2351.
42. Mursinna RS, Lincecum TL, Martinis SA. 2001. A conserved threonine within Escherichia coli leucyl-tRNA synthetase prevents hydrolytic editing of leucyl-tRNALeu. Biochemistry (Mosc) 40:5376-5381. http://dx.doi.org/10.1021/bi002915w.
43. Seiradake E, Mao W, Hernandez V, Baker SJ, Plattner JJ, Alley MRK, Cusack S. 2009. Crystal structures of the human and fungal cytosolic leucyl-tRNA synthetase editing domains: a structural basis for the rational design of antifungal benzoxaboroles. J Mol Biol 390:196-207. http://dx.doi.org/10.1016/j.jmb.2009.04.073.
44. Dosztányi Z, Csizmok V, Tompa P, Simon I. 2005. IUPred: web server for the prediction of intrinsically unstructured regions of proteins based on estimated energy content. Bioinformatics 21:3433-3434. http://dx.doi.org/10.1093/bioinformatics/bti541.
45. Cvetesic N, Palencia A, Halasz I, Cusack S, Gruic-Sovulj I. 2014. The physiological target for LeuRS translational quality control is norvaline. EMBO J 33:1639-1653. http://dx.doi.org/10.15252/embj.201488199.
46. Hussain T, Kamarthapu V, Kruparani SP, Deshmukh MV, Sankaranarayanan R. 2010. Mechanistic insights into cognate substrate discrimination during proofreading in translation. Proc Natl Acad Sci U S A 107: 22117-22121. http://dx.doi.org/10.1073/pnas.1014299107.
47. Ladbury JE, Klebe G, Freire E. 2010. Adding calorimetric data to decision making in lead discovery: a hot tip. Nat Rev Drug Discov 9:23-27. http://dx.doi.org/10.1038/nrd3054.
48. Velázquez Campoy A, Freire E. 2005. ITC in the post-genomic era? Priceless. Biophys Chem 115:115-124. http://dx.doi.org/10.1016/j.bpc .2004.12.015.
49. Liu Y, Liao J, Zhu B, Wang E-D, Ding J. 2006. Crystal structures of the editing domain of Escherichia coli leucyl-tRNA synthetase and its complexes with Met and Ile reveal a lock-and-key mechanism for amino acid discrimination. Biochem J 394:399-407. http://dx.doi.org/10.1042/BJ20051249.
50. Guo M, Yang X-L, Schimmel P. 2010. New functions of aminoacyl-tRNA synthetases beyond translation. Nat Rev Mol Cell Biol 11:668-674. http://dx.doi.org/10.1038/nrm2956.
51. Yao P, Fox PL. 2013. Aminoacyl-tRNA synthetases in medicine and disease. EMBO Mol Med 5:332-343. http://dx.doi.org/10.1002/emmm .201100626.
52. Lincecum TL, Tukalo M, Yaremchuk A, Mursinna RS, Williams AM, Sproat BS, Van Den Eynde W, Link A, Van Calenbergh S, Grøtli M, Martinis SA, Cusack S. 2003. Structural and mechanistic basis of pre-and posttransfer editing by leucyl-tRNA synthetase. Mol Cell 11:951-963. http://dx.doi.org/10.1016/S1097-2765(03)00098-4.
53. Hagiwara Y, Field MJ, Nureki O, Tateno M. 2010. Editing mechanism of aminoacyl-tRNA synthetases operates by a hybrid ribozyme/protein catalyst. J Am Chem Soc 132:2751-2758. http://dx.doi.org/10.1021/ja9095208.
54. Dock-Bregeon A, Sankaranarayanan R, Romby P, Caillet J, Springer M, Rees B, Francklyn CS, Ehresmann C, Moras D. 2000. Transfer RNAmediated editing in threonyl-tRNA synthetase. The class II solution to the double discrimination problem. Cell 103:877-884.
55. Sankaranarayanan R, Dock-Bregeon AC, Rees B, Bovee M, Caillet J, Romby P, Francklyn CS, Moras D. 2000. Zinc ion mediated amino acid discrimination by threonyl-tRNA synthetase. Nat Struct Biol 7:461-465. http://dx.doi.org/10.1038/75856.
56. Soini J, Falschlehner C, Liedert C, Bernhardt J, Vuoristo J, Neubauer P. 2008. Norvaline is accumulated after a down-shift of oxygen in Escherichia coli W3110. Microb Cell Fact 7:30. http://dx.doi.org/10.1186/1475-2859-7-30.
57. Hu Q-H, Liu R-J, Fang Z-P, Zhang J, Ding Y-Y, Tan M, Wang M, Pan W, Zhou H-C, Wang E-D. 2013. Discovery of a potent benzoxaborolebased anti-pneumococcal agent targeting leucyl-tRNA synthetase. Sci Rep 3:2475. http://dx.doi.org/10.1038/srep02475.
58. Jain V, Yogavel M, Oshima Y, Kikuchi H, Touquet B, Hakimi M-A, Sharma A. 2015. Structure of prolyl-tRNA synthetase-halofuginone complex provides basis for development of drugs against malaria and toxoplasmosis. Structure 23:819-829. http://dx.doi.org/10.1016/j.str.2015.02 .011.
59. Keller TL, Zocco D, Sundrud MS, Hendrick M, Edenius M, Yum J, Kim Y-J, Lee H-K, Cortese JF, Wirth DF, Dignam JD, Rao A, Yeo C-Y, Mazitschek R, Whitman M. 2012. Halofuginone and other febrifugine derivatives inhibit prolyl-tRNA synthetase. Nat Chem Biol 8:311-317. http://dx.doi.org/10.1038/nchembio.790.
60. Zhou H, Sun L, Yang X-L, Schimmel P. 2013. ATP-directed capture of bioactive herbal-based medicine on human tRNA synthetase. Nature 494: 121-124. http://dx.doi.org/10.1038/nature11774.
61. Zhu S, Wang J, Chandrashekar G, Smith E, Liu X, Zhang Y. 2010. Synthesis and evaluation of 4-quinazolinone compounds as potential antimalarial agents. Eur J Med Chem 45:3864-3869. http://dx.doi.org/10 .1016/j.ejmech.2010.05.040.
62. Hoen R, Novoa EM, López A, Camacho N, Cubells L, Vieira P, Santos M, Marin-Garcia P, Bautista JM, Cortés A, Ribas de Pouplana L, Royo M. 2013. Selective inhibition of an apicoplastic aminoacyl-tRNA synthetase from Plasmodium falciparum. Chembiochem 14:499-509. http://dx.doi.org/10.1002/cbic.201200620.
63. Hoepfner D, McNamara CW, Lim CS, Studer C, Riedl R, Aust T, McCormack SL, Plouffe DM, Meister S, Schuierer S, Plikat U, Hartmann N, Staedtler F, Cotesta S, Schmitt EK, Petersen F, Supek F, Glynne RJ, Tallarico JA, Porter JA, Fishman MC, Bodenreider C, Diagana TT, Movva NR, Winzeler EA. 2012. Selective and specific inhibition of the Plasmodium falciparum lysyl-tRNA synthetase by the fungal secondary metabolite cladosporin. Cell Host Microbe 11:654-663. http://dx.doi.org/10.1016/j.chom.2012.04.015.
64. Istvan ES, Dharia NV, Bopp SE, Gluzman I, Winzeler EA, Goldberg DE. 2011. Validation of isoleucine utilization targets in Plasmodium falciparum. Proc Natl Acad Sci U S A 108:1627-1632. http://dx.doi.org/10.1073/pnas.1011560108.
65. Liu J, Istvan ES, Gluzman IY, Gross J, Goldberg DE. 2006. Plasmodium falciparum ensures its amino acid supply with multiple acquisition pathways and redundant proteolytic enzyme systems. Proc Natl Acad SciUSA 103:8840-8845. http://dx.doi.org/10.1073/pnas.0601876103.
66. Ciaravino V, Plattner J, Chanda S. 2013. An assessment of the genetic toxicology of novel boron-containing therapeutic agents. Environ Mol Mutagen 54:338-346. http://dx.doi.org/10.1002/em.21779.