In vitro and in vivo effects of the bumped kinase inhibitor 1294 in the related cyst-forming apicomplexans Toxoplasma gondii and Neospora caninum

Antimicrobial Agents and Chemotherapy

Volumn 59, Issue 10, 2015, Pages 6361-6374

  Winzer, Pablo ^a   Müller, Joachim ^a   Aguado Martínez, Adriana ^a   Rahman, Mahbubur ^a   Balmer, Vreni ^a   Manser, Vera ^a   Ortega Mora, Luis Miguel ^b   Ojo, Kayode K ^c   Fan, Erkang ^c   Maly, Dustin J ^d   Van Voorhis, Wesley C ^c   Hemphill, Andrew ^a  

^a UNIVERSITY OF BERN   (Switzerland)

^b UNIVERSIDAD COMPLUTENSE DE MADRID   (Spain)

^c UNIVERSITY OF WASHINGTON SCHOOL OF MEDICINE   (United States)

^d UNIVERSITY OF WASHINGTON   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ANTIPROTOZOAL AGENT; BAG1 PROTEIN; BKI 1294; MESSENGER RNA; MONOCLONAL ANTIBODY; MONOCLONAL ANTIBODY CC2; PHOSPHOTRANSFERASE INHIBITOR; SAG1 PROTEIN; UNCLASSIFIED DRUG; BAG1 PROTEIN, TOXOPLASMA; CALCIUM-DEPENDENT PROTEIN KINASE; COCCIDIOSTATIC AGENT; HEAT SHOCK PROTEIN; PARASITE ANTIGEN; PROTEIN KINASE; PROTEIN KINASE INHIBITOR; PROTOZOAL PROTEIN; SAG1 ANTIGEN, TOXOPLASMA; SAG1 PROTEIN, NEOSPORA CANINUM;

ANIMAL EXPERIMENT; ANTIGEN EXPRESSION; ARTICLE; CONTROLLED STUDY; DRUG EFFICACY; FEMALE; FIBROBLAST; HUMAN; HUMAN CELL; IC50; IMMUNOFLUORESCENCE; IN VITRO STUDY; IN VIVO STUDY; MALE; MOUSE; NEOSPORA CANINUM; NEOSPOROSIS; NONHUMAN; PARASITE LOAD; PARASITE VIRULENCE; PRIORITY JOURNAL; PROTEIN EXPRESSION; REAL TIME POLYMERASE CHAIN REACTION; TACHYZOITE; TOXOPLASMA GONDII; TOXOPLASMOSIS; VERTICAL TRANSMISSION; AGONISTS; ANIMAL; ANTAGONISTS AND INHIBITORS; BAGG ALBINO MOUSE; COCCIDIOSIS; DRUG EFFECTS; ENZYMOLOGY; GENE EXPRESSION; GENETICS; METABOLISM; NEOSPORA; PARASITOLOGY; PREGNANCY; PREVENTION AND CONTROL; PRIMARY CELL CULTURE; TOXOPLASMA; TRANSMISSION;

ANIMALS; ANTIBODIES, MONOCLONAL; ANTIGENS, PROTOZOAN; COCCIDIOSIS; COCCIDIOSTATS; FEMALE; FIBROBLASTS; GENE EXPRESSION; HEAT-SHOCK PROTEINS; HUMANS; INFECTIOUS DISEASE TRANSMISSION, VERTICAL; MICE; MICE, INBRED BALB C; NEOSPORA; PREGNANCY; PRIMARY CELL CULTURE; PROTEIN KINASE INHIBITORS; PROTEIN KINASES; PROTOZOAN PROTEINS; RNA, MESSENGER; TOXOPLASMA; TOXOPLASMOSIS;

EID: 84942911911     PISSN: 00664804     EISSN: 10986596     Source Type: Journal    
DOI: 10.1128/AAC.01236-15     Document Type: Article

References (50)

1. Lim SS, Othman RY. 2014. Recent advances in Toxoplasma gondii immunotherapeutics. Korean J Parasitol 52:581-593. http://dx.doi.org/10.3347/kjp. 2014.52.6.581.
2. Campos FA, Andrade GM, Lanna Ade P, Lage BF, Assumpcao MV, Pinto JA. 2014. Incidence of congenital toxoplasmosis among infants born to HIV-coinfected mothers: case series and literature review. Braz J Infect Dis 18:609-617. http://dx.doi.org/10.1016/j.bjid.2014.05.008.
3. Monney T, Hemphill A. 2014. Vaccines against neosporosis: what can we learn from the past studies? Exp Parasitol 140:52-70. http://dx.doi.org/10.1016/j.exppara.2014.02.015.
4. Reichel MP, Alejandra Ayanegui-Alcerreca M, Gondim LF, Ellis JT. 2013. What is the global economic impact of Neospora caninum in cattle-the billion dollar question. Int J Parasitol 43:133-142. http://dx.doi.org/10.1016/j.ijpara.2012.10.022.
5. Dubey JP, Schares G, Ortega-Mora LM. 2007. Epidemiology and control of neosporosis and Neospora caninum. Clin Microbiol Rev 20:323-367. http://dx.doi.org/10.1128/CMR.00031-06.
6. Ojo KK, Pfander C, Mueller NR, Burstroem C, Larson ET, Bryan CM, Fox AM, Reid MC, Johnson SM, Murphy RC, Kennedy M, Mann H, Leibly DJ, Hewitt SN, Verlinde CL, Kappe S, Merritt EA, Maly DJ, Billker O, Van Voorhis WC. 2012. Transmission of malaria to mosquitoes blocked by bumped kinase inhibitors. J Clin Invest 122:2301-2305. http://dx.doi.org/10.1172/JCI61822.
7. Lendner M, Bottcher D, Delling C, Ojo KK, Van Voorhis WC, Daugschies A. 2015. A novel CDPK1 inhibitor-a potential treatment for cryptosporidiosis in calves? Parasitol Res 114:335-336. http://dx.doi.org/10.1007/s00436-014-4228-7.
8. Castellanos-Gonzalez A, White AC, Jr, Ojo KK, Vidadala RS, Zhang Z, Reid MC, Fox AM, Keyloun KR, Rivas K, Irani A, Dann SM, Fan E, Maly DJ, Van Voorhis WC. 2013. A novel calcium-dependent protein kinase inhibitor as a lead compound for treating cryptosporidiosis. J Infect Dis 208:1342-1348. http://dx.doi.org/10.1093/infdis/jit327.
9. Checkley W, White AC, Jr, Jaganath D, Arrowood MJ, Chalmers RM, Chen XM, Fayer R, Griffiths JK, Guerrant RL, Hedstrom L, Huston CD, Kotloff KL, Kang G, Mead JR, Miller M, Petri WA, Jr, Priest JW, Roos DS, Striepen B, Thompson RC, 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.
10. Ojo KK, Reid MC, Kallur Siddaramaiah L, Müller J, Winzer P, Zhang Z, Keyloun KR, Vidadala RS, Merritt EA, Hol WG, Maly DJ, Fan E, Van Voorhis WC, Hemphill A. 2014. Neospora caninum calcium-dependent protein kinase 1 is an effective drug target for neosporosis therapy. PLoS One 9:e92929. http://dx.doi.org/10.1371/journal.pone.0092929.
11. Keyloun KR, Reid MC, Choi R, Song Y, Fox AM, Hillesland HK, Zhang Z, Vidadala R, Merritt EA, Lau AO, Maly DJ, Fan E, Barrett LK, Van Voorhis WC, Ojo KK. 2014. The gatekeeper residue and beyond: homologous calcium-dependent protein kinases as drug development targets for veterinarian Apicomplexa parasites. Parasitology 141:1499-1509. http://dx.doi.org/10.1017/S0031182014000857.
12. Ojo KK, Larson ET, Keyloun KR, Castaneda LJ, Derocher AE, Inampudi KK, Kim JE, Arakaki TL, Murphy RC, Zhang L, Napuli AJ, Maly DJ, Verlinde CL, Buckner FS, Parsons M, Hol WG, Merritt EA, Van Voorhis WC. 2010. Toxoplasma gondii calcium-dependent protein kinase 1 is a target for selective kinase inhibitors. Nat Struct Mol Biol 17:602-607. http://dx.doi.org/10.1038/nsmb.1818.
13. Sugi T, Kawazu S, Horimoto T, Kato K. 2015. A single mutation in the gatekeeper residue in TgMAPKL-1 restores the inhibitory effect of a bumped kinase inhibitor on the cell cycle. Int J Parasitol Drugs Drug Resist 5:1-8. http://dx.doi.org/10.1016/j.ijpddr.2014.12.001.
14. Barna F, Debache K, Vock CA, Küster T, Hemphill A. 2013. In vitro effects of novel ruthenium complexes in Neospora caninum and Toxoplasma gondii tachyzoites. Antimicrob Agents Chemother 57:5747-5754. http://dx.doi.org/10.1128/AAC.02446-12.
15. Schorer M, Debache K, Barna F, Monney T, Müller J, Boykin DW, Stephens CE, Hemphill A. 2012. Di-cationic arylimidamides act against Neospora caninum tachyzoites by interference in membrane structure and nucleolar integrity and are active against challenge infection in mice. Int J Parasitol Drugs Drug Resist 2:109-120. http://dx.doi.org/10.1016/j.ijpddr.2012.03.001.
16. Hemphill A, Gottstein B, Kaufmann H. 1996. Adhesion and invasion of bovine endothelial cells by Neospora caninum. Parasitology 112:183-197.
17. Kropf C, Debache K, Rampa C, Barna F, Schorer M, Stephens CE, Ismail MA, Boykin DW, Hemphill A. 2012. The adaptive potential of a survival artist: characterization of the in vitro interactions of Toxoplasma gondii tachyzoites with di-cationic compounds in human fibroblast cell cultures. Parasitology 139:208-220. http://dx.doi.org/10.1017/S0031182011001776.
18. Alaeddine F, Hemphill A, Debache K, Guionaud C. 2013. Molecular cloning and characterization of NcROP2Fam-1, a member of the ROP2 family of rhoptry proteins in Neospora caninum that is targeted by antibodies neutralizing host cell invasion in vitro. Parasitology 140:1033-1050. http://dx.doi.org/10.1017/S0031182013000383.
19. Guionaud C, Hemphill A, Mevissen M, Alaeddine F. 2010. Molecular characterization of Neospora caninum MAG1, a dense granule protein secreted into the parasitophorous vacuole, and associated with the cyst wall and the cyst matrix. Parasitology 137:1605-1619. http://dx.doi.org/10.1017/S0031182010000442.
20. Gross U, Bormuth H, Gaissmaier C, Dittrich C, Krenn V, Bohne W, Ferguson DJ. 1995. Monoclonal rat antibodies directed against Toxoplasma gondii suitable for studying tachyzoite-bradyzoite interconversion in vivo. Clin Diagn Lab Immunol 2:542-548.
21. Vonlaufen N, Guetg N, Naguleswaran A, Müller N, Bjorkman C, Schares G, Von Blumroeder D, Ellis J, Hemphill A. 2004. In vitro induction of Neospora caninum bradyzoites in Vero cells reveals differential antigen expression, localization, and host-cell recognition of tachyzoites and bradyzoites. Infect Immun 72:576-583. http://dx.doi.org/10.1128/IAI.72.1.576-583.2004.
22. Vonlaufen N, Müller N, Keller N, Naguleswaran A, Bohne W, McAllister MM, Bjorkman C, Muller E, Caldelari R, Hemphill A. 2002. Exogenous nitric oxide triggers Neospora caninum tachyzoite-tobradyzoite stage conversion in murine epidermal keratinocyte cell cultures. Int J Parasitol 32:1253-1265. http://dx.doi.org/10.1016/S0020-7519 (02) 00126-1.
23. McAllister MM, Parmley SF, Weiss LM, Welch VJ, McGuire AM. 1996. An immunohistochemical method for detecting bradyzoite antigen (BAG5) in Toxoplasma gondii-infected tissues cross-reacts with a Neospora caninum bradyzoite antigen. J Parasitol 82:354-355. http://dx.doi.org/10.2307/3284181.
24. Bjorkman C, Hemphill A. 1998. Characterization of Neospora caninum iscom antigens using monoclonal antibodies. Parasite Immunol 20:73-80. http://dx.doi.org/10.1046/j.1365-3024.1998.00127.x.
25. Monney T, Grandgirard D, Leib SL, Hemphill A. 2013. Use of a Th1 stimulator adjuvant for vaccination against Neospora caninum infection in the pregnant mouse model. Pathogens 2:193-208. http://dx.doi.org/10.3390/pathogens2020193.
26. Arranz-Solís D, Aguado-Martínez A, Müller J, Regidor-Cerrillo J, Ortega-Mora LM, Hemphill A. 2015. Dose-dependent effects of experimental infection with the virulent Neospora caninum Nc-Spain7 isolate in a pregnant mouse model. Vet Parasitol 211:133-140. http://dx.doi.org/10.1016/j.vetpar.2015.05.021.
27. Müller J, Aguado-Martinez A, Manser V, Balmer V, Winzer P, Ritler D, Hostettler I, Arranz-Solís D, Ortega-Mora L, Hemphill A. 2015. Buparvaquone is active against Neospora caninum in vitro and in experimentally infected mice. Int J Parasitol Drugs Drug Resist 5:16-25. http://dx.doi.org/10.1016/j.ijpddr.2015.02.001.
28. Debache K, Alaeddine F, Guionaud C, Monney T, Müller J, Strohbusch M, Leib SL, Grandgirard D, Hemphill A. 2009. Vaccination with recombinant NcROP2 combined with recombinant NcMIC1 and NcMIC3 reduces cerebral infection and vertical transmission in mice experimentally infected with Neospora caninum tachyzoites. Int J Parasitol 39:1373-1384. http://dx.doi.org/10.1016/j.ijpara.2009.04.006.
29. Debache K, Guionaud C, Alaeddine F, Mevissen M, Hemphill A. 2008. Vaccination of mice with recombinant NcROP2 antigen reduces mortality and cerebral infection in mice infected with Neospora caninum tachyzoites. Int J Parasitol 38:1455-1463. http://dx.doi.org/10.1016/j.ijpara.2008.04.001.
30. Core Team R. 2012. R: a language and environment for statistical computing. The R Foundation for Statistical Computing, Vienna, Austria.
31. Bohne W, Gross U, Ferguson DJ, Heesemann J. 1995. Cloning and characterization of a bradyzoite-specifically expressed gene (hsp30/bag1) of Toxoplasma gondii, related to genes encoding small heat-shock proteins of plants. Mol Microbiol 16:1221-1230. http://dx.doi.org/10.1111/j.1365-2958.1995.tb02344.x.
32. Jacot D, Soldati-Favre D. 2012. Does protein phosphorylation govern host cell entry and egress by the Apicomplexa? Int J Med Microbiol 302:195-202. http://dx.doi.org/10.1016/j.ijmm.2012.07.012.
33. Wei F, Wang W, Liu Q. 2013. Protein kinases of Toxoplasma gondii: functions and drug targets. Parasitol Res 112:2121-2129. http://dx.doi.org/10.1007/s00436-013-3451-y.
34. Harper JF, Harmon A. 2005. Plants, symbiosis and parasites: a calcium signalling connection. Nat Rev Mol Cell Biol 6:555-566. http://dx.doi.org/10.1038/nrm1679.
35. Kieschnick H, Wakefield T, Narducci CA, Beckers C. 2001. Toxoplasma gondii attachment to host cells is regulated by a calmodulin-like domain protein kinase. J Biol Chem 276:12369-12377. http://dx.doi.org/10.1074/jbc. M011045200.
36. Lourido S, Shuman J, Zhang C, Shokat KM, Hui R, Sibley LD. 2010. Calcium-dependent protein kinase 1 is an essential regulator of exocytosis in Toxoplasma. Nature 465:359-362. http://dx.doi.org/10.1038/nature09022.
37. Larson ET, Ojo KK, Murphy RC, Johnson SM, Zhang Z, Kim JE, Leibly DJ, Fox AM, Reid MC, Dale EJ, Perera BG, Kim J, Hewitt SN, Hol WG, Verlinde CL, Fan E, Van Voorhis WC, Maly DJ, Merritt EA. 2012. Multiple determinants for selective inhibition of apicomplexan calciumdependent protein kinase CDPK1. J Med Chem 55:2803-2810. http://dx.doi.org/10.1021/jm201725v.
38. Lourido S, Zhang C, Lopez MS, Tang K, Barks J, Wang Q, Wildman SA, Shokat KM, Sibley LD. 2013. Optimizing small molecule inhibitors of calcium-dependent protein kinase 1 to prevent infection by Toxoplasma gondii. J Med Chem 56:3068-3077. http://dx.doi.org/10.1021/jm4001314.
39. Johnson SM, Murphy RC, Geiger JA, De Rocher AE, Zhang Z, Ojo KK, Larson ET, Perera BG, Dale EJ, He P, Reid MC, Fox AM, Mueller NR, Merritt EA, Fan E, Parsons M, Van Voorhis WC, Maly DJ. 2012. Development of Toxoplasma gondii calcium-dependent protein kinase 1 (TgCDPK1) inhibitors with potent anti-toxoplasma activity. J Med Chem 55:2416-2426. http://dx.doi.org/10.1021/jm201713h.
40. Zhang Z, Ojo KK, Vidadala R, Huang W, Geiger JA, Scheele S, Choi R, Reid MC, Keyloun KR, Rivas K, Siddaramaiah LK, Comess KM, Robinson KP, Merta PJ, Kifle L, Hol WG, Parsons M, Merritt EA, Maly DJ, Verlinde CL, Van Voorhis WC, Fan E. 2014. Potent and selective inhibitors of CDPK1 from and based on a 5-aminopyrazole-4-carboxamide scaffold. ACS Med Chem Lett 5:40-44. http://dx.doi.org/10.1021/ml400315s.
41. Zhang Z, Ojo KK, Johnson SM, Larson ET, He P, Geiger JA, Castellanos-Gonzalez A, White AC, Jr, Parsons M, Merritt EA, Maly DJ, Verlinde CL, Van Voorhis WC, Fan E. 2012. Benzoylbenzimidazolebased selective inhibitors targeting Cryptosporidium parvum and Toxoplasma gondii calcium-dependent protein kinase-1. Bioorg Med Chem Lett 22:5264-5267. http://dx.doi.org/10.1016/j.bmcl.2012.06.050.
42. Murphy RC, Ojo KK, Larson ET, Castellanos-Gonzalez A, Perera BG, Keyloun KR, Kim JE, Bhandari JG, Muller NR, Verlinde CL, White AC, Jr, Merritt EA, Van Voorhis WC, Maly DJ. 2010. Discovery of potent and selective inhibitors of calcium-dependent protein kinase 1 (CDPK1) from C. parvum and T. gondii. ACS Med Chem Lett 1:331-335. http://dx.doi.org/10.1021/ml100096t.
43. Brown KM, Suvorova E, Farrell A, McLain A, Dittmar A, Wiley GB, Marth G, Gaffney PM, Gubbels MJ, White M, Blader IJ. 2014. Forward genetic screening identifies a small molecule that blocks Toxoplasma gondii growth by inhibiting both host- and parasite-encoded kinases. PLoS Pathog 10:e1004180. http://dx.doi.org/10.1371/journal.ppat.1004180.
44. Wei S, Marches F, Daniel B, Sonda S, Heidenreich K, Curiel T. 2002. Pyridinylimidazole p38 mitogen-activated protein kinase inhibitors block intracellular Toxoplasma gondii replication. Int J Parasitol 32:969-977. http://dx.doi.org/10.1016/S0020-7519 (02) 00061-9.
45. Sugi T, Masatani T, Murakoshi F, Kawazu S, Kato K. 2014. Microplate assay for screening Toxoplasma gondii bradyzoite differentiation with DUAL luciferase assay. Anal Biochem 464:9-11. http://dx.doi.org/10.1016/j.ab.2014.06.018.
46. Dzierszinski F, Nishi M, Ouko L, Roos DS. 2004. Dynamics of Toxoplasma gondii differentiation. Eukaryot Cell 3:992-1003. http://dx.doi.org/10.1128/EC.3.4.992-1003.2004.
47. Sugi T, Kobayashi K, Takemae H, Gong H, Ishiwa A, Murakoshi F, Recuenco FC, Iwanaga T, Horimoto T, Akashi H, Kato K. 2013. Identification of mutations in TgMAPK1 of Toxoplasma gondii conferring resistance to 1NM-PP1. Int J Parasitol Drugs Drug Resist 3:93-101. http://dx.doi.org/10.1016/j.ijpddr.2013.04.001.
48. Ojo KK, Eastman RT, Vidadala R, Zhang Z, Rivas KL, Choi R, Lutz JD, Reid MC, Fox AM, Hulverson MA, Kennedy M, Isoherranen N, Kim LM, Comess KM, Kempf DJ, Verlinde CL, Su XZ, Kappe SH, Maly DJ, Fan E, Van Voorhis WC. 2014. A specific inhibitor of PfCDPK4 blocks malaria transmission: chemical-genetic validation. J Infect Dis 209:275-284. http://dx.doi.org/10.1093/infdis/jit522.
49. Doggett JS, Ojo KK, Fan E, Maly DJ, Van Voorhis WC. 2014. Bumped kinase inhibitor 1294 treats established Toxoplasma gondii infection. Antimicrob Agents Chemother 58:3547-3549. http://dx.doi.org/10.1128/AAC.01823-13.
50. Sugi T, Kato K, Kobayashi K, Kurokawa H, Takemae H, Gong H, Recuenco FC, Iwanaga T, Horimoto T, Akashi H. 2011. 1NM-PP1 treatment of mice infected with Toxoplasma gondii. J Vet Med Sci 73:1377-1379. http://dx.doi.org/10.1292/jvms.11-0085.