Structural basis for selective targeting of leishmanial ribosomes: Aminoglycoside derivatives as promising therapeutics

Nucleic Acids Research

Volumn 43, Issue 17, 2015, Pages 8601-8613

  Shalev, Moran ^a,b   Rozenberg, Haim ^b   Smolkin, Boris ^a   Nasereddin, Abedelmajeed ^c   Kopelyanskiy, Dmitry ^c   Belakhov, Valery ^a   Schrepfer, Thomas ^d   Schacht, Jochen ^d   Jaffe, Charles L ^c   Adir, Noam ^a   Baasov, Timor ^a  

^a TECHNION ISRAEL INSTITUTE OF TECHNOLOGY   (Israel)

^b WEIZMANN INSTITUTE OF SCIENCE   (Israel)

^c HEBREW UNIVERSITY OF JERUSALEM   (Israel)

^d UNIVERSITY OF MICHIGAN MEDICAL SCHOOL   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

AMINOGLYCOSIDE DERIVATIVE; GENTAMICIN; PAROMOMYCIN; RIBOSOME RNA; ANTIPROTOZOAL AGENT; NEOMYCIN; PROTEIN SYNTHESIS INHIBITOR;

ANTIPROTOZOAL ACTIVITY; ARTICLE; BINDING AFFINITY; BINDING SITE; CONCENTRATION RESPONSE; CRYSTALLIZATION; DRUG EFFICACY; DRUG STRUCTURE; GROWTH INHIBITION; IC50; LEISHMANIA DONOVANI; LEISHMANIA MAJOR; LIGAND BINDING; MICROBIAL GROWTH; OTOTOXICITY; PRIORITY JOURNAL; RETICULOCYTE; RIBOSOME; RNA RECOMBINATION; SENSORY NERVE CELL; VISCERAL LEISHMANIASIS; ANALOGS AND DERIVATIVES; ANIMAL; CELL LINE; CHEMISTRY; COMPUTER SIMULATION; DRUG EFFECTS; GROWTH, DEVELOPMENT AND AGING; GUINEA PIG; HUMAN; LEISHMANIA; MACROPHAGE; MALE; MOLECULAR MODEL; PARASITOLOGY; PROTEIN SYNTHESIS;

ANIMALS; ANTIPROTOZOAL AGENTS; BINDING SITES; CELL LINE; COMPUTER SIMULATION; GUINEA PIGS; HUMANS; LEISHMANIA; MACROPHAGES; MALE; MODELS, MOLECULAR; NEOMYCIN; PAROMOMYCIN; PROTEIN BIOSYNTHESIS; PROTEIN SYNTHESIS INHIBITORS; RIBOSOMES; RNA, RIBOSOMAL;

EID: 84949033503     PISSN: 03051048     EISSN: 13624962     Source Type: Journal    
DOI: 10.1093/nar/gkv821     Document Type: Article

References (59)

1. Second WHO report on neglecteg tropical diseases. (2013) pp. 67-71.
2. Moore, T.A. (2005) Agents used to treat infections due to parasites and pneumocystis. In: Kasper, DL (ed). Harrison's Principles of Internal Medicine, 16th edn. Mc Graw Hill, Vol. 1, pp. 1202-1214.
3. Neal, R.A. (1968) The effect of antibiotics of the neomycin group on experimental cutaneous leishmaniasis. Ann. Trop. Med. Parasitol., 62, 54-62.
4. Ben, S.A., Ben, M.N., Guedri, E., Zaatour, A., Ben, A.N., Bettaieb, J., Gharbi, A., Belhadj, H.N., Boukthir, A., Chlif, S. et al. (2013) Topical paromomycin with or without gentamicin for cutaneous leishmaniasis.N. Engl. J. Med., 368, 524-532.
5. Lecoeur, H., Buffet, P.A., Milon, G. and Lang, T. (2010) Early curative applications of the aminoglycoside WR279396 on an experimental Leishmania major-loaded cutaneous site do not impair the acquisition of immunity. Antimicrob. Agents Chemother., 54, 984-990.
6. El-On, J., Weinrauch, L., Livshin, R., Even-Paz, Z. and Jacobs, G.P. (1985) Topical treatment of recurrent cutaneous leishmaniasis with ointment containing paromomycin and methylbenzethonium chloride. Br. Med. J. (Clin. Res. Ed.), 291, 704-705.
7. Sundar, S., Jha, T.K., Thakur, C.P., Sinha, P.K. and Bhattacharya, S.K. (2007) Injectable paromomycin for Visceral leishmaniasis in India. N. Engl. J. Med., 356, 2571-2581.
8. WHO model list of essential medicines. (2007). 17th edn. 15.
9. Sundar, S. and Chakravarty, J. (2013) Leishmaniasis: an update of current pharmacotherapy. Expert. Opin. Pharmacother., 14, 53-63.
10. Sundar, S., Sinha, P.K., Rai, M., Verma, D.K., Nawin, K., Alam, S., Chakravarty, J., Vaillant, M., Verma, N., Pandey, K. et al. (2011) Comparison of short-course multidrug treatment with standard therapy for visceral leishmaniasis in India: an open-label, non-inferiority, randomised controlled trial. Lancet, 377, 477-486.
11. Maarouf, M., de, K.Y., Brown, S., Petit, P.X. and Robert-Gero, M. (1997) In vivo interference of paromomycin with mitochondrial activity of Leishmania. Exp. Cell Res., 232, 339-348.
12. Fernandez, M.M., Malchiodi, E.L. and Algranati, I.D. (2011) Differential effects of paromomycin on ribosomes of Leishmania mexicana and mammalian cells. Antimicrob. Agents Chemother., 55, 86-93.
13. Hobbie, S.N., Kaiser, M., Schmidt, S., Shcherbakov, D., Janusic, T., Brun, R. and Bottger, E.C. (2011) Genetic reconstruction of protozoan rRNA decoding sites provides a rationale for paromomycin activity against Leishmania and Trypanosoma. PLoS Negl. Trop. Dis., 5, e1161.
14. Maarouf, M., Lawrence, F., Croft, S.L. and Robert-Gero, M. (1995) Ribosomes of Leishmania are a target for the aminoglycosides. Parasitol. Res., 81, 421-425.
15. Shalev, M., Kondo, J., Kopelyanskiy, D., Jaffe, C.L., Adir, N. and Baasov, T. (2013) Identification of the molecular attributes required for aminoglycoside activity against Leishmania. Proc. Natl. Acad. Sci. U.S.A., 110, 13333-13338.
16. Kandasamy, J., Atia-Glikin, D., Shulman, E., Shapira, K., Shavit, M., Belakhov, V. and Baasov, T. (2012) Increased selectivity toward cytoplasmic versus mitochondrial ribosome confers improved efficiency of synthetic aminoglycosides in fixing damaged genes: a strategy for treatment of genetic diseases caused by nonsense mutations. J. Med. Chem., 55, 10630-10643.
17. Kondo, J., Hainrichson, M., Nudelman, I., Shallom-Shezifi, D., Barbieri, C.M., Pilch, D.S., Westhof, E. and Baasov, T. (2007) Differential selectivity of natural and synthetic aminoglycosides towards the eukaryotic and prokaryotic decoding A sites. Chembiochem., 8, 1700-1709.
18. Nudelman, I., Rebibo-Sabbah, A., Shallom-Shezifi, D., Hainrichson, M., Stahl, I., Ben-Yosef, T. and Baasov, T. (2006) Redesign of aminoglycosides for treatment of human genetic diseases caused by premature stop mutations. Bioorg. Med. Chem. Lett., 16, 6310-6315.
19. Nudelman, I., Rebibo-Sabbah, A., Cherniavsky, M., Belakhov, V., Hainrichson, M., Chen, F., Schacht, J., Pilch, D.S., Ben-Yosef, T. and Baasov, T. (2009) Development of novel aminoglycoside (NB54) with reduced toxicity and enhanced suppression of disease-causing premature stop mutations. J. Med. Chem., 52, 2836-2845.
20. Nudelman, I., Glikin, D., Smolkin, B., Hainrichson, M., Belakhov, V. and Baasov, T. (2010) Repairing faulty genes by aminoglycosides: development of new derivatives of geneticin (G418) with enhanced suppression of diseases-causing nonsense mutations. Bioorg. Med. Chem., 18, 3735-3746.
21. Berger, I., Kang, C.H., Sinha, N., Wolters, M. and Rich, A. (1996) A highly efficient 24-condition matrix for the crystallization of nucleic acid fragments. Acta Crystallogr. D Biol. Crystallogr., 52, 465-468.
22. Kabsch, W. (2010) XDS. Acta Crystallogr. D Biol. Crystallogr., 66, 125-132.
23. Adams, P.D., Afonine, P.V., Bunkoczi, G., Chen, V.B., Davis, I.W., Echols, N., Headd, J.J., Hung, L.W., Kapral, G.J., Grosse-Kunstleve, R.W. et al. (2010) PHENIX: a comprehensive Python-based system for macromolecular structure solution. Acta Crystallogr. D Biol. Crystallogr., 66, 213-221.
24. Emsley, P. and Cowtan, K. (2004) Coot: model-building tools for molecular graphics. Acta Crystallogr. D Biol. Crystallogr., 60, 2126-2132.
25. The PyMol Molecular Graphics System. (2010) Schrödinger, LLC, V.1.5.0.4.S.L.
26. Leatherbarrow, R.J. (2001) GraFit. Erithacus Software Ltd. Horley, Vol. 5.
27. Trott, O. and Olson, A.J. (2010) AutoDock Vina: improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading. J Comput. Chem., 31, 455-461.
28. Morris, G.M., Huey, R., Lindstrom, W., Sanner, M.F., Belew, R.K., Goodsell, D.S. and Olson, A.J. (2009) AutoDock4 and AutoDockTools4: Automated docking with selective receptor flexibility. J Comput. Chem., 30, 2785-2791.
29. Aghdam, E.M., Hejazi, M.S. and Barzegar, A. (2014) Riboswitches as potential targets for aminoglycosides in comparing with rRNA molecules: in silico study. Microb. Biochem. Technol., 9, S9.
30. Francois, B., Szychowski, J., Adhikari, S.S., Pachamuthu, K., Swayze, E.E., Griffey, R.H., Migawa, M.T., Westhof, E. and Hanessian, S. (2004) Antibacterial aminoglycosides with a modified mode of binding to the ribosomal-RNA decoding site. Angew. Chem. Int. Ed. Engl., 43, 6735-6738.
31. Francois, B., Russell, R.J., Murray, J.B., Aboul-ela, F., Masquida, B., Vicens, Q. and Westhof, E. (2005) Crystal structures of complexes between aminoglycosides and decoding A site oligonucleotides: role of the number of rings and positive charges in the specific binding leading to miscoding. Nucleic Acids Res., 33, 5677-5690.
32. Hermann, T., Tereshko, V., Skripkin, E. and Patel, D.J. (2007) Apramycin recognition by the human ribosomal decoding site. Blood Cells Mol. Dis., 38, 193-198.
33. Kondo, J., Francois, B., Urzhumtsev, A. and Westhof, E. (2005) Crystallographic studies of Homo sapiens ribosomal decoding A site complexed with aminoglycosides. Nucleic Acids Symp. Ser. (Oxf.), 49, 253-254.
34. Kondo, J., Francois, B., Urzhumtsev, A. and Westhof, E. (2006) Crystal structure of the Homo sapiens cytoplasmic ribosomal decoding site complexed with apramycin. Angew. Chem. Int. Ed. Engl., 45, 3310-3314.
35. Kondo, J., Pachamuthu, K., Francois, B., Szychowski, J., Hanessian, S. and Westhof, E. (2007) Crystal structure of the bacterial ribosomal decoding site complexed with a synthetic doubly functionalized paromomycin derivative: a new specific binding mode to an a-minor motif enhances in vitro antibacterial activity. ChemMedChem, 2, 1631-1638.
36. Vicens, Q. and Westhof, E. (2001) Crystal structure of paromomycin docked into the eubacterial ribosomal decoding A site. Structure, 9, 647-658.
37. Vicens, Q. and Westhof, E. (2002) Crystal structure of a complex between the aminoglycoside tobramycin and an oligonucleotide containing the ribosomal decoding a site. Chem. Biol., 9, 747-755.
38. Vicens, Q. and Westhof, E. (2003) Crystal structure of geneticin bound to a bacterial 16S ribosomal RNA A site oligonucleotide. J Mol. Biol., 326, 1175-1188.
39. Carter, A.P., Clemons, W.M., Brodersen, D.E., Morgan-Warren, R.J., Wimberly, B.T. and Ramakrishnan, V. (2000) Functional insights from the structure of the 30S ribosomal subunit and its interactions with antibiotics. Nature, 407, 340-348.
40. Ogle, J.M., Brodersen, D.E., Clemons, W.M. Jr, Tarry, M.J., Carter, A.P. and Ramakrishnan, V. (2001) Recognition of cognate transfer RNA by the 30S ribosomal subunit. Science, 292, 897-902.
41. Ogle, J.M., Murphy, F.V., Tarry, M.J. and Ramakrishnan, V. (2002) Selection of tRNA by the ribosome requires a transition from an open to a closed form. Cell, 111, 721-732.
42. Ogle, J.M. and Ramakrishnan, V. (2005) Structural insights into translational fidelity. Annu. Rev. Biochem., 74, 129-177.
43. Kondo, J., Urzhumtsev, A. and Westhof, E. (2006) Two conformational states in the crystal structure of the Homo sapiens cytoplasmic ribosomal decoding A site. Nucleic Acids Res., 34, 676-685.
44. Kondo, J. and Westhof, E. (2008) The bacterial and mitochondrial ribosomal A-site molecular switches possess different conformational substates. Nucleic Acids Res., 36, 2654-2666.
45. Simonsen, K.B., Ayida, B.K., Vourloumis, D., Takahashi, M., Winters, G.C., Barluenga, S., Qamar, S., Shandrick, S., Zhao, Q. and Hermann, T. (2002) Novel paromamine derivatives exploring shallow-groove recognition of ribosomal-decoding-site RNA. Chembiochem, 3, 1223-1228.
46. Garreau de, L.N., Prokhorova, I., Holtkamp, W., Rodnina, M.V., Yusupova, G. and Yusupov, M. (2014) Structural basis for the inhibition of the eukaryotic ribosome. Nature, 513, 517-522.
47. Kondo, J., Koganei, M., Maianti, J.P., Ly, V.L. and Hanessian, S. (2013) Crystal structures of a bioactive 6'-hydroxy variant of sisomicin bound to the bacterial and protozoal ribosomal decoding sites. ChemMedChem, 8, 733-739.
48. Maianti, J.P., Kanazawa, H., Dozzo, P., Matias, R.D., Feeney, L.A., Armstrong, E.S., Hildebrandt, D.J., Kane, T.R., Gliedt, M.J., Goldblum, A.A. et al. (2014) Toxicity modulation, resistance enzyme evasion, and A-site X-ray structure of broad-spectrum antibacterial neomycin analogs. ACS Chem. Biol., 9, 2067-2073.
49. Szychowski, J., Kondo, J., Zahr, O., Auclair, K., Westhof, E., Hanessian, S. and Keillor, J.W. (2011) Inhibition of aminoglycoside-deactivating enzymes APH(3')-IIIa and AAC(6')-Ii by amphiphilic paromomycin O2"-ether analogues. ChemMedChem, 6, 1961-1966.
50. Kondo, J. (2012) A structural basis for the antibiotic resistance conferred by an A1408G mutation in 16S rRNA and for the antiprotozoal activity of aminoglycosides. Angew. Chem. Int. Ed. Engl., 51, 465-468.
51. Shulman, E., Belakhov, V., Wei, G., Kendall, A., Meyron-Holtz, E.G., Ben-Shachar, D., Schacht, J. and Baasov, T. (2014) Designer aminoglycosides that selectively inhibit cytoplasmic rather than mitochondrial ribosomes show decreased ototoxicity: a strategy for the treatment of genetic diseases. J Biol. Chem., 289, 2318-2330.
52. Jhingran, A., Chawla, B., Saxena, S., Barrett, M.P. and Madhubala, R. (2009) Paromomycin: uptake and resistance in Leishmania donovani. Mol. Biochem. Parasitol., 164, 111-117.
53. Forge, A. and Schacht, J. (2000) Aminoglycoside antibiotics. Audiol. Neurootol., 5, 3-22.
54. Duggal, P. and Sarkar, M. (2007) Audiologic monitoring of multi-drug resistant tuberculosis patients on aminoglycoside treatment with long term follow-up. BMC Ear Nose Throat Disord., 7, 5.
55. Hobbie, S.N., Akshay, S., Kalapala, S.K., Bruell, C.M., Shcherbakov, D. and Bottger, E.C. (2008) Genetic analysis of interactions with eukaryotic rRNA identify the mitoribosome as target in aminoglycoside ototoxicity. Proc. Natl. Acad. Sci. U.S.A., 105, 20888-20893.
56. Matt, T., Ng, C.L., Lang, K., Sha, S.H., Akbergenov, R., Shcherbakov, D., Meyer, M., Duscha, S., Xie, J., Dubbaka, S.R. et al. (2012) Dissociation of antibacterial activity and aminoglycoside ototoxicity in the 4-monosubstituted 2-deoxystreptamine apramycin. Proc. Natl. Acad. Sci. U.S.A., 109, 10984-10989.
57. Xue, X., Mutyam, V., Tang, L., Biswas, S., Du, M., Jackson, L.A., Dai, Y., Belakhov, V., Shalev, M., Chen, F. et al. (2014) Synthetic aminoglycosides efficiently suppress cystic fibrosis transmembrane conductance regulator nonsense mutations and are enhanced by ivacaftor. Am. J Respir. Cell Mol. Biol., 50, 805-816.
58. Manzo, E. and Mea, O. (1967) [Ototoxicity of aminosidine. II. Histological studies in the guinea pig]. Arch. Ital. Laringol., 75, 189-199.
59. Musa, A., Khalil, E., Hailu, A., Olobo, J., Balasegaram, M., Omollo, R., Edwards, T., Rashid, J., Mbui, J., Musa, B. et al. (2012) Sodium stibogluconate (SSG) & paromomycin combination compared to SSG for visceral leishmaniasis in East Africa: a randomised controlled trial. PLoS Negl. Trop. Dis., 6, e1674.