Parasitology Research

, Volume 112, Issue 5, pp 1819–1831 | Cite as

Current drug targets for helminthic diseases

Review

Abstract

More than 2 billion people are infected with helminth parasites across the globe. The burgeoning drug resistance against current anthelmintics in parasitic worms of humans and livestock requires urgent attention to tackle these recalcitrant worms. This review focuses on the advancements made in the area of helminth drug target discovery especially from the last few couple of decades. It highlights various approaches made in this field and enlists the potential drug targets currently being pursued to target economically important helminth species both from human as well as livestock to combat disease pathology of schistosomiasis, onchocerciasis, lymphatic filariasis, and other important macroparasitic diseases. Research in the helminths study is trending to identify potential and druggable targets through genomic, proteomic, biochemical, biophysical, in vitro experiments, and in vivo experiments in animal models. The availability of major helminths genome sequences and the subsequent availability of genome-scale functional datasets through in silico search and prioritization are expected to guide the experimental work necessary for target-based drug discovery. Organized and documented list of drug targets from various helminths of economic importance have been systematically covered in this review for further exploring their use and applications, which can give physicians and veterinarians effective drugs in hand to enable them control worm infections.

References

  1. Abubucker S, Martin J, Taylor CM, Mitreva M (2011) HelmCoP: an online resource for helminth functional genomics and drug and vaccine targets prioritization. PLoS One 6(7):e21832. doi:10.1371/journal.pone.0021832 PubMedCrossRefGoogle Scholar
  2. Allen JE et al (2008) Of mice, cattle, and humans: the immunology and treatment of river blindness. PLoS Negl Trop Dis 2(4):e217. doi:10.1371/journal.pntd.0000217 PubMedCrossRefGoogle Scholar
  3. Alvarez LI, Mottier ML, Lanusse CE (2007) Drug transfer into target helminth parasites. Trends Parasitol 23(3):97–104. doi:10.1016/j.pt.2007.01.003 PubMedCrossRefGoogle Scholar
  4. Andrade LF, et al. (2011) Eukaryotic protein kinases (ePKs) of the helminth parasite Schistosoma mansoni. BMC Genomics 12:215 doi:10.1186/1471-2164-12-215
  5. Angelucci F, et al. (2009) Inhibition of Schistosoma mansoni thioredoxin-glutathione reductase by auranofin: structural and kinetic aspects. J Biol Chem 284(42):28977-85 doi:10.1074/jbc.M109.020701 Google Scholar
  6. Aranzamendi C, Sofronic-Milosavljevic L, Pinelli E (2013) Helminths: immunoregulation and inflammatory diseases—which side are Trichinella spp. and Toxocara spp. on? J Parasitol Res 2013:329438PubMedGoogle Scholar
  7. Awasthi SK et al (2009) Antifilarial activity of 1,3-diarylpropen-1-one: effect on glutathione-S-transferase, a phase II detoxification enzyme. AmJTrop Med Hyg 80(5):764–768Google Scholar
  8. Beech RN, Skuce P, Bartley DJ, Martin RJ, Prichard RK, Gilleard JS (2011) Anthelmintic resistance: markers for resistance, or susceptibility? Parasitology 138(2):160–174. doi:10.1017/S0031182010001198 PubMedCrossRefGoogle Scholar
  9. Bonilla M, Denicola A, Marino SM, Gladyshev VN, Salinas G (2011) Linked thioredoxin-glutathione systems in platyhelminth parasites: alternative pathways for glutathione reduction and deglutathionylation. J Biol Chem 286(7):4959–4967. doi:10.1074/jbc.M110.170761 PubMedCrossRefGoogle Scholar
  10. Boumis G, Angelucci F, Bellelli A, Brunori M, Dimastrogiovanni D, Miele AE (2011) Structural and functional characterization of Schistosoma mansoni thioredoxin. Protein Sci 20(6):1069–1076. doi:10.1002/pro.634 PubMedCrossRefGoogle Scholar
  11. Brooker S et al (2009) An updated atlas of human helminth infections: the example of East Africa. Int J Health Geogr 8:42. doi:10.1186/1476-072X-8-42 PubMedCrossRefGoogle Scholar
  12. Brophy PM, MacKintosh N, Morphew RM (2012) Anthelmintic metabolism in parasitic helminths: proteomic insights. Parasitology 139(9):1205–1217. doi:10.1017/S003118201200087X PubMedCrossRefGoogle Scholar
  13. Carre-Pierrat M et al (2006) The SLO-1 BK channel of Caenorhabditis elegans is critical for muscle function and is involved in dystrophin-dependent muscle dystrophy. J Mol Biol 358(2):387–395. doi:10.1016/j.jmb.2006.02.037 PubMedCrossRefGoogle Scholar
  14. Chambers E et al (2010) Liver fluke beta-tubulin isotype 2 binds albendazole and is thus a probable target of this drug. Parasitol Res 107(5):1257–1264. doi:10.1007/s00436-010-1997-5 PubMedCrossRefGoogle Scholar
  15. Chen M et al (2009) The anti-helminthic niclosamide inhibits Wnt/Frizzled1 signaling. Biochemistry 48(43):10267–10274. doi:10.1021/bi9009677 PubMedCrossRefGoogle Scholar
  16. Chen W et al (2011) Molecular characterization of cathepsin B from Clonorchis sinensis excretory/secretory products and assessment of its potential for serodiagnosis of clonorchiasis. Parasit Vectors 4:149. doi:10.1186/1756-3305-4-149 PubMedCrossRefGoogle Scholar
  17. Christensen NO, Nansen P, Fagbemi BO, Monrad J (1987) Heterologous antagonistic and synergistic interactions between helminths and between helminths and protozoans in concurrent experimental infection of mammalian hosts. Parasitol Res 73(5):387–410PubMedCrossRefGoogle Scholar
  18. Chuan J et al (2010) Our wormy world genomics, proteomics and transcriptomics in east and southeast Asia. Adv Parasitol 73:327–371. doi:10.1016/S0065-308X(10)73011-6 PubMedCrossRefGoogle Scholar
  19. Crisford A et al (2011) Selective toxicity of the anthelmintic emodepside revealed by heterologous expression of human KCNMA1 in Caenorhabditis elegans. Mol Pharmacol 79(6):1031–1043. doi:10.1124/mol.111.071043 PubMedCrossRefGoogle Scholar
  20. Crowther GJ et al (2010) Identification of attractive drug targets in neglected-disease pathogens using an in silico approach. PLoS Negl Trop Dis 4(8):e804. doi:10.1371/journal.pntd.0000804 PubMedCrossRefGoogle Scholar
  21. Dangi A, Dwivedi V, Vedi S, Owais M, Misra-Bhattacharya S (2009) Improvement in the antifilarial efficacy of doxycycline and rifampicin by combination therapy and drug delivery approach. J Drug Target 18(5):343–350. doi:10.3109/10611860903450007 CrossRefGoogle Scholar
  22. de Silva NR, Brooker S, Hotez PJ, Montresor A, Engels D, Savioli L (2003) Soil-transmitted helminth infections: updating the global picture. Trends Parasitol 19(12):547–551PubMedCrossRefGoogle Scholar
  23. Doenhoff MJ, Cioli D, Utzinger J (2008) Praziquantel: mechanisms of action, resistance and new derivatives for schistosomiasis. Curr Opin Infect Dis 21(6):659–667. doi:10.1097/QCO.0b013e328318978f PubMedCrossRefGoogle Scholar
  24. Eweas AF, Allam G, Abuelsaad AS, Alghamdi AH, Maghrabi IA (2012) Design, synthesis, anti-schistosomal activity and molecular docking of novel 8-hydroxyquinoline-5-sufonyl 1,4-diazepine derivatives. Bioorg Chem 46:17–25. doi:10.1016/j.bioorg.2012.10.003 PubMedCrossRefGoogle Scholar
  25. Fontana AC et al (2009) Two allelic isoforms of the serotonin transporter from Schistosoma mansoni display electrogenic transport and high selectivity for serotonin. Eur J Pharmacol 616(1–3):48–57. doi:10.1016/j.ejphar.2009.06.023 PubMedCrossRefGoogle Scholar
  26. Foster J et al (2005) The Wolbachia genome of Brugia malayi: endosymbiont evolution within a human pathogenic nematode. PLoS Biol 3(4):e121. doi:10.1371/journal.pbio.0030121 PubMedCrossRefGoogle Scholar
  27. Foster JM, Raverdy S, Ganatra MB, Colussi PA, Taron CH, Carlow CK (2009) The Wolbachia endosymbiont of Brugia malayi has an active phosphoglycerate mutase: a candidate target for anti-filarial therapies. Parasitol Res 104(5):1047–1052. doi:10.1007/s00436-008-1287-7 PubMedCrossRefGoogle Scholar
  28. Gasbarre LC (1997) Effects of gastrointestinal nematode infection on the ruminant immune system. Vet Parasitol 72(3–4):327–337, discussion 337–43PubMedCrossRefGoogle Scholar
  29. Geadkaew A, von Bulow J, Beitz E, Grams SV, Viyanant V, Grams R (2010) Functional analysis of novel aquaporins from Fasciola gigantica. Mol Biochem Parasitol 175(2):144–153. doi:10.1016/j.molbiopara.2010.10.010 PubMedCrossRefGoogle Scholar
  30. Gelmedin V, Caballero-Gamiz R, Brehm K (2008) Characterization and inhibition of a p38-like mitogen-activated protein kinase (MAPK) from Echinococcus multilocularis: antiparasitic activities of p38 MAPK inhibitors. Biochem Pharmacol 76(9):1068–81. doi:10.1016/j.bcp.2008.08.020 Google Scholar
  31. Guest M et al (2007) The calcium-activated potassium channel, SLO-1, is required for the action of the novel cyclo-octadepsipeptide anthelmintic, emodepside, in Caenorhabditis elegans. Int J Parasitol 37(14):1577–1588. doi:10.1016/j.ijpara.2007.05.006 PubMedCrossRefGoogle Scholar
  32. Hagen J, Lee EF, Fairlie WD, Kalinna BH (2011) Functional genomics approaches in parasitic helminths. Parasite Immunol 34(2–3):163–182. doi:10.1111/j.1365-3024.2011.01306.x Google Scholar
  33. Halton DW (2004) Microscopy and the helminth parasite. Micron 35(5):361–390. doi:10.1016/j.micron.2003.12.001 PubMedCrossRefGoogle Scholar
  34. Hanelt B et al (2010) Schistosomes of small mammals from the Lake Victoria Basin, Kenya: new species, familiar species, and implications for schistosomiasis control. Parasitology 137(7):1109–1118. doi:10.1017/S0031182010000041 PubMedCrossRefGoogle Scholar
  35. Hibbs RE, Gouaux E (2011) Principles of activation and permeation in an anion-selective Cys-loop receptor. Nature 474(7349):54–60. doi:10.1038/nature10139 PubMedCrossRefGoogle Scholar
  36. Holroyd N, Sanchez-Flores A (2012) Producing parasitic helminth reference and draft genomes at the Wellcome Trust Sanger Institute. Parasite Immunol 34(2–3):100–107. doi:10.1111/j.1365-3024.2011.01311.x PubMedCrossRefGoogle Scholar
  37. Hong Y et al (2012) Characterization and expression of the Schistosoma japonicum thioredoxin peroxidase-2 gene. J Parasitol 99(1):68–76. doi:10.1645/GE-3096.1 PubMedCrossRefGoogle Scholar
  38. Horn M, Jilkova A, Vondrasek J, Maresova L, Caffrey CR, Mares M (2011) Mapping the pro-peptide of the Schistosoma mansoni cathepsin B1 drug target: modulation of inhibition by heparin and design of mimetic inhibitors. ACS Chem Biol 6(6):609–617. doi:10.1021/cb100411v PubMedCrossRefGoogle Scholar
  39. Hotez PJ, Brindley PJ, Bethony JM, King CH, Pearce EJ, Jacobson J (2008) Helminth infections: the great neglected tropical diseases. J Clin Invest 118(4):1311–1321. doi:10.1172/JCI34261 PubMedCrossRefGoogle Scholar
  40. Hotez PJ et al (2007) Control of neglected tropical diseases. N Engl J Med 357(10):1018–1027. doi:10.1056/NEJMra064142 PubMedCrossRefGoogle Scholar
  41. Hotez PJ, Molyneux DH, Fenwick A, Ottesen E, Ehrlich Sachs S, Sachs JD (2006) Incorporating a rapid-impact package for neglected tropical diseases with programs for HIV/AIDS, tuberculosis, and malaria. PLoS Med 3(5):e102. doi:10.1371/journal.pmed.0030102 PubMedCrossRefGoogle Scholar
  42. Hu Y, Platzer EG, Bellier A, Aroian RV (2010) Discovery of a highly synergistic anthelmintic combination that shows mutual hypersusceptibility. Proc Natl Acad Sci U S A 107(13):5955–5960. doi:10.1073/pnas.0912327107 PubMedCrossRefGoogle Scholar
  43. Hu Y, Xiao SH, Aroian RV (2009) The new anthelmintic tribendimidine is an L-type (levamisole and pyrantel) nicotinic acetylcholine receptor agonist. PLoS Negl Trop Dis 3(8):e499. doi:10.1371/journal.pntd.0000499 PubMedCrossRefGoogle Scholar
  44. Huang J, Huang Y, Wu X, Du W, Yu X, Hu X (2009) Identification, expression, characterization, and immunolocalization of lactate dehydrogenase from Taenia asiatica. Parasitol Res 104(2):287–293. doi:10.1007/s00436-008-1190-2 PubMedCrossRefGoogle Scholar
  45. Huang Y et al (2012) Identification and characterization of myophilin-like protein: a life stage and tissue-specific antigen of Clonorchis sinensis. Parasitol Res 111(3):1143–1150. doi:10.1007/s00436-012-2946-2 PubMedCrossRefGoogle Scholar
  46. James CE, Hudson AL, Davey MW (2009) Drug resistance mechanisms in helminths: is it survival of the fittest? Trends Parasitol 25(7):328–335. doi:10.1016/j.pt.2009.04.004 PubMedCrossRefGoogle Scholar
  47. Jilkova A et al (2011) Structural basis for inhibition of cathepsin B drug target from the human blood fluke, Schistosoma mansoni. J Biol Chem 286(41):35770–35781. doi:10.1074/jbc.M111.271304 PubMedCrossRefGoogle Scholar
  48. Johnston KL, Wu B, Guimaraes A, Ford L, Slatko BE, Taylor MJ (2010) Lipoprotein biosynthesis as a target for anti-Wolbachia treatment of filarial nematodes. Parasit Vectors 3:99. doi:10.1186/1756-3305-3-99 PubMedCrossRefGoogle Scholar
  49. Jones PM, George AM (2005) Multidrug resistance in parasites: ABC transporters, P-glycoproteins and molecular modelling. Int J Parasitol 35(5):555–566. doi:10.1016/j.ijpara.2005.01.012 PubMedCrossRefGoogle Scholar
  50. Kaletta T, Hengartner MO (2006) Finding function in novel targets: C. elegans as a model organism. Nat Rev Drug Discov 5(5):387–398. doi:10.1038/nrd2031 PubMedCrossRefGoogle Scholar
  51. Kaminsky R et al (2008) A new class of anthelmintics effective against drug-resistant nematodes. Nature 452(7184):176–180. doi:10.1038/nature06722 PubMedCrossRefGoogle Scholar
  52. Kawasaki I, Jeong MH, Oh BK, Shim YH (2010) Apigenin inhibits larval growth of Caenorhabditis elegans through DAF-16 activation. FEBS Lett 584(16):3587–3591. doi:10.1016/j.febslet.2010.07.026 PubMedCrossRefGoogle Scholar
  53. Keiser J, Utzinger J (2010) The drugs we have and the drugs we need against major helminth infections. Adv Parasitol 73:197–230. doi:10.1016/S0065-308X(10)73008-6 PubMedCrossRefGoogle Scholar
  54. Khanim FL et al (2011) Redeployment-based drug screening identifies the anti-helminthic niclosamide as anti-myeloma therapy that also reduces free light chain production. Blood Cancer J 1(10):e39. doi:10.1038/bcj.2011.38 PubMedCrossRefGoogle Scholar
  55. Kita K, Nihei C, Tomitsuka E (2003) Parasite mitochondria as drug target: diversity and dynamic changes during the life cycle. Curr Med Chem 10(23):2535–2548PubMedCrossRefGoogle Scholar
  56. Kozak M, Kolodziej-Sobocinska M (2009) Progress in the development of vaccines against helminths. Wiad Parazytol 55(2):147–156PubMedGoogle Scholar
  57. Kruger N, Harder A, von Samson-Himmelstjerna G (2009) The putative cyclooctadepsipeptide receptor depsiphilin of the canine hookworm Ancylostoma caninum. Parasitol Res 105(Suppl 1):S91–S100. doi:10.1007/s00436-009-1500-3 PubMedCrossRefGoogle Scholar
  58. Kumar A, Saxena JK, Chauhan PM (2008) Synthesis of 4-amino-5-cyano-2, 6-disubstituted pyrimidines as a potential antifilarial DNA topoisomerase II inhibitors. Med Chem 4(6):577–585PubMedCrossRefGoogle Scholar
  59. Kumar S et al (2007) Mining predicted essential genes of Brugia malayi for nematode drug targets. PLoS One 2(11):e1189. doi:10.1371/journal.pone.0001189 PubMedCrossRefGoogle Scholar
  60. Kushwaha S, Singh PK, Rana AK, Misra-Bhattacharya S (2011) Cloning, expression, purification and kinetics of trehalose-6-phosphate phosphatase of filarial parasite Brugia malayi. Acta Trop 119(2–3):151–159. doi:10.1016/j.actatropica.2011.05.008 PubMedCrossRefGoogle Scholar
  61. Kushwaha S, Singh PK, Shahab M, Pathak M, Bhattacharya SM (2012) In vitro silencing of Brugia malayi trehalose-6-phosphate phosphatase impairs embryogenesis and in vivo development of infective larvae in jirds. PLoS Negl Trop Dis 6(8):e1770. doi:10.1371/journal.pntd.0001770 PubMedCrossRefGoogle Scholar
  62. Lee EF et al (2011) Discovery and molecular characterization of a Bcl-2-regulated cell death pathway in schistosomes. Proc Natl Acad Sci U S A 108(17):6999–7003. doi:10.1073/pnas.1100652108 PubMedCrossRefGoogle Scholar
  63. Lees K, Sluder A, Shannan N, Hammerland L, Sattelle D (2012) Ligand-Gated Ion Channels as Targets for Anthelmintic Drugs: Past, Current, and Future Perspectives, in Parasitic Helminths: Targets, Screens, Drugs and Vaccines. Wiley-VCH Verlag GmbH & Co, KGaA, Weinheim, Germany. doi:10.1002/9783527652969.ch1 Google Scholar
  64. Li HF et al (2010) Wnt4, the first member of the Wnt family identified in Schistosoma japonicum, regulates worm development by the canonical pathway. Parasitol Res 107(4):795–805. doi:10.1007/s00436-010-1933-8 PubMedCrossRefGoogle Scholar
  65. Li Z, Garner AL, Gloeckner C, Janda KD, Carlow CK (2011) Targeting the Wolbachia cell division protein FtsZ as a new approach for antifilarial therapy. PLoS Negl Trop Dis 5(11):e1411. doi:10.1371/journal.pntd.0001411 PubMedCrossRefGoogle Scholar
  66. Lin J, Sahakian DC, de Morais SM, Xu JJ, Polzer RJ, Winter SM (2003) The role of absorption, distribution, metabolism, excretion and toxicity in drug discovery. Curr Top Med Chem 3(10):1125–1154PubMedCrossRefGoogle Scholar
  67. Liu J et al (2012) Molecular cloning and characterization of Schistosoma japonicum aldose reductase. Parasitol Res 112(2):549–558. doi:10.1007/s00436-012-3166-5 PubMedCrossRefGoogle Scholar
  68. Long T et al (2010) Schistosoma mansoni Polo-like kinase 1: a mitotic kinase with key functions in parasite reproduction. Int J Parasitol 40(9):1075–1086. doi:10.1016/j.ijpara.2010.03.002 PubMedCrossRefGoogle Scholar
  69. Long T et al (2012) SmSak, the second Polo-like kinase of the helminth parasite Schistosoma mansoni: conserved and unexpected roles in meiosis. PLoS One 7(6):e40045. doi:10.1371/journal.pone.0040045 PubMedCrossRefGoogle Scholar
  70. Lu G et al (2006) Expression and characterization of lactate dehydrogenase from Schistosoma japonicum. Parasitol Res 99(5):593–596. doi:10.1007/s00436-006-0152-9 PubMedCrossRefGoogle Scholar
  71. Marks NJ, Maule AG (2010) Neuropeptides in helminths: occurrence and distribution. Adv Exp Med Biol 692:49–77PubMedCrossRefGoogle Scholar
  72. Martin J, Abubucker S, Heizer E, Taylor CM, Mitreva M (2011) Nematode.net update 2011: addition of data sets and tools featuring next-generation sequencing data. Nucleic Acids Res 40(Database issue):D720-8 doi:10.1093/nar/gkr1194
  73. Martinez-Gonzalez JJ, Guevara-Flores A, Alvarez G, Rendon-Gomez JL, Del Arenal IP (2010) In vitro killing action of auranofin on Taenia crassiceps metacestode (cysticerci) and inactivation of thioredoxin-glutathione reductase (TGR). Parasitol Res 107(1):227–231. doi:10.1007/s00436-010-1867-1 PubMedCrossRefGoogle Scholar
  74. Marxer M, Ingram K, Keiser J (2012) Development of an in vitro drug screening assay using Schistosoma haematobium schistosomula. Parasit Vectors 5:165. doi:10.1186/1756-3305-5-165 PubMedCrossRefGoogle Scholar
  75. McCavera S, Rogers AT, Yates DM, Woods DJ, Wolstenholme AJ (2009) An ivermectin-sensitive glutamate-gated chloride channel from the parasitic nematode Haemonchus contortus. Mol Pharmacol 75(6):1347–1355. doi:10.1124/mol.108.053363 PubMedCrossRefGoogle Scholar
  76. McVeigh P et al (2009) Discovery of multiple neuropeptide families in the phylum Platyhelminthes. Int J Parasitol 39(11):1243–1252. doi:10.1016/j.ijpara.2009.03.005 PubMedCrossRefGoogle Scholar
  77. Misra-Bhattacharya S, Katiyar D, Bajpai P, Tripathi RP, Saxena JK (2004) 4-Methyl-7-(tetradecanoyl)-2H-1-benzopyran-2-one: a novel DNA topoisomerase II inhibitor with adulticidal and embryostatic activity against sub-periodic Brugia malayi. Parasitol Res 92(3):177–182. doi:10.1007/s00436-003-1014-3 PubMedCrossRefGoogle Scholar
  78. Misra S, Verma M, Mishra SK, Srivastava S, Lakshmi V, Misra-Bhattacharya S (2011) Gedunin and photogedunin of Xylocarpus granatum possess antifilarial activity against human lymphatic filarial parasite Brugia malayi in experimental rodent host. Parasitol Res 109(5):1351–1360. doi:10.1007/s00436-011-2380-x PubMedCrossRefGoogle Scholar
  79. Modis Y (2012) Exploiting structural biology in the fight against parasitic diseases. Trends Parasitol. doi:10.1016/j.pt.2012.01.003
  80. Mousley A, Novozhilova E, Kimber MJ, Day TA (2010) Neuropeptide physiology in helminths. Adv Exp Med Biol 692:78–97PubMedCrossRefGoogle Scholar
  81. Muhlfeld S, Schmitt-Wrede HP, Harder A, Wunderlich F (2009) FMRFamide-like neuropeptides as putative ligands of the latrophilin-like HC110-R from Haemonchus contortus. Mol Biochem Parasitol 164(2):162–164. doi:10.1016/j.molbiopara.2008.12.003 PubMedCrossRefGoogle Scholar
  82. Mutapi F (2012) Helminth parasite proteomics: from experimental models to human infections. Parasitology 139(9):1195–1204. doi:10.1017/S0031182011002423 PubMedCrossRefGoogle Scholar
  83. Nogi T, Zhang D, Chan JD, Marchant JS (2009) A novel biological activity of praziquantel requiring voltage-operated Ca2+ channel beta subunits: subversion of flatworm regenerative polarity. PLoS Negl Trop Dis 3(6):e464. doi:10.1371/journal.pntd.0000464 PubMedCrossRefGoogle Scholar
  84. Omura S et al (2001) An anthelmintic compound, nafuredin, shows selective inhibition of complex I in helminth mitochondria. Proc Natl Acad Sci U S A 98(1):60–62. doi:10.1073/pnas.011524698 PubMedCrossRefGoogle Scholar
  85. Osei-Atweneboana MY, Lustigman S, Prichard RK, Boatin BA, Basanez MG (2012) A research agenda for helminth diseases of humans: health research and capacity building in disease-endemic countries for helminthiases control. PLoS Negl Trop Dis 6(4):e1602. doi:10.1371/journal.pntd.0001602 PubMedCrossRefGoogle Scholar
  86. Otero L, Bonilla M, Protasio AV, Fernandez C, Gladyshev VN, Salinas G (2010) Thioredoxin and glutathione systems differ in parasitic and free-living platyhelminths. BMC Genomics 11:237. doi:10.1186/1471-2164-11-237 PubMedCrossRefGoogle Scholar
  87. Parker GA, Chubb JC, Ball MA, Roberts GN (2003) Evolution of complex life cycles in helminth parasites. Nature 425(6957):480–484. doi:10.1038/nature02012 PubMedCrossRefGoogle Scholar
  88. Peng J, Han H, Hong Y, Fu Z, Liu J, Lin J (2010a) Molecular cloning and characterization of a gene encoding methionine aminopeptidase 2 of Schistosoma japonicum. Parasitol Res 107(4):939–946. doi:10.1007/s00436-010-1956-1 PubMedCrossRefGoogle Scholar
  89. Peng J, Yang Y, Feng X, Cheng G, Lin J (2010b) Molecular characterizations of an inhibitor of apoptosis from Schistosoma japonicum. Parasitol Res 106(4):967–976. doi:10.1007/s00436-010-1752-y PubMedCrossRefGoogle Scholar
  90. Pierson L, Mousley A, Devine L, Marks NJ, Day TA, Maule AG (2009) RNA interference in a cestode reveals specific silencing of selected highly expressed gene transcripts. Int J Parasitol 40(5):605–615. doi:10.1016/j.ijpara.2009.10.012 PubMedCrossRefGoogle Scholar
  91. Prichard RK et al (2012) A research agenda for helminth diseases of humans: intervention for control and elimination. PLoS Negl Trop Dis 6(4):e1549. doi:10.1371/journal.pntd.0001549 PubMedCrossRefGoogle Scholar
  92. Rapsch C et al (2008) An interactive map to assess the potential spread of Lymnaea truncatula and the free-living stages of Fasciola hepatica in Switzerland. Vet Parasitol 154(3–4):242–249. doi:10.1016/j.vetpar.2008.03.030 PubMedCrossRefGoogle Scholar
  93. Ribeiro-dos-Santos G, Verjovski-Almeida S, Leite LC (2006) Schistosomiasis—a century searching for chemotherapeutic drugs. Parasitol Res 99(5):505–521. doi:10.1007/s00436-006-0175-2 PubMedCrossRefGoogle Scholar
  94. Robertson AP, Martin RJ (2007) Ion-channels on parasite muscle: pharmacology and physiology. Invert Neurosci 7(4):209–217. doi:10.1007/s10158-007-0059-x PubMedCrossRefGoogle Scholar
  95. Rufener L, Maser P, Roditi I, Kaminsky R (2009) Haemonchus contortus acetylcholine receptors of the DEG-3 subfamily and their role in sensitivity to monepantel. PLoS Pathog 5(4):e1000380. doi:10.1371/journal.ppat.1000380 PubMedCrossRefGoogle Scholar
  96. Sakai C, Tomitsuka E, Esumi H, Harada S, Kita K (2011) Mitochondrial fumarate reductase as a target of chemotherapy: from parasites to cancer cells. Biochim Biophys Acta. doi:10.1016/j.bbagen.2011.12.013
  97. Salvador-Recatala V, Greenberg RM (2010) The N terminus of a schistosome beta subunit regulates inactivation and current density of a Cav2 channel. J Biol Chem 285(46):35878–35888. doi:10.1074/jbc.M110.144725 PubMedCrossRefGoogle Scholar
  98. Singh M, Srivastava KK, Bhattacharya SM (2009) Molecular cloning and characterization of a novel immunoreactive ATPase/RNA helicase in human filarial parasite Brugia malayi. Parasitol Res 104(4):753–761. doi:10.1007/s00436-008-1251-6 PubMedCrossRefGoogle Scholar
  99. Sivasamy R, Angayarkanni J, Palaniswamy M (2011) A novel filarial topoisomerase II inhibitor produced by native isolateMicrococcus luteus B1252. Afr J Biotechnol 10(71):16069–16077CrossRefGoogle Scholar
  100. Skinner DE et al (2012) Vasa-Like DEAD-Box RNA Helicases of Schistosoma mansoni. PLoS Negl Trop Dis 6(6):e1686. doi:10.1371/journal.pntd.0001686 PubMedCrossRefGoogle Scholar
  101. Song C, Gallup JM, Day TA, Bartholomay LC, Kimber MJ (2011) Development of an in vivo RNAi protocol to investigate gene function in the filarial nematode, Brugia malayi. PLoS Pathog 6(12):e1001239. doi:10.1371/journal.ppat.1001239 CrossRefGoogle Scholar
  102. Spiliotis M, Brehm K (2009) Axenic in vitro cultivation of Echinococcus multilocularis metacestode vesicles and the generation of primary cell cultures. Methods Mol Biol 470:245–62 doi:10.1007/978-1-59745-204-5_17 Google Scholar
  103. Srinivasan L, Mathew N, Muthuswamy K (2009) In vitro antifilarial activity of glutathione S-transferase inhibitors. Parasitol Res 105(4):1179–1182. doi:10.1007/s00436-009-1534-6 PubMedCrossRefGoogle Scholar
  104. Tandon R, LePage KT, Kaplan RM (2006) Cloning and characterization of genes encoding alpha and beta subunits of glutamate-gated chloride channel protein in Cylicocyclus nassatus. Mol Biochem Parasitol 150(1):46–55. doi:10.1016/j.molbiopara.2006.06.007 PubMedCrossRefGoogle Scholar
  105. Taylor CM et al (2011) Targeting protein–protein interactions for parasite control. PLoS One 6(4):e18381. doi:10.1371/journal.pone.0018381 PubMedCrossRefGoogle Scholar
  106. Verma S, Robertson AP, Martin RJ (2007) The nematode neuropeptide, AF2 (KHEYLRF-NH2), increases voltage-activated calcium currents in Ascaris suum muscle. Br J Pharmacol 151(6):888–899. doi:10.1038/sj.bjp.0707296 PubMedCrossRefGoogle Scholar
  107. Von Brand T (1948) The physiology of helminth parasites in relation to disease. Abstr Int Congr Trop Med Malar 56(4th Congr):77Google Scholar
  108. Wang LJ, Cao Y, Shi HN (2008) Helminth infections and intestinal inflammation. World J Gastroenterol 14(33):5125–5132PubMedCrossRefGoogle Scholar
  109. Wang Z et al (2009) Identification of the nuclear receptor DAF-12 as a therapeutic target in parasitic nematodes. Proc Natl Acad Sci U S A 106(23):9138–9143. doi:10.1073/pnas.0904064106 PubMedCrossRefGoogle Scholar
  110. Welz C et al (2011) SLO-1-channels of parasitic nematodes reconstitute locomotor behaviour and emodepside sensitivity in Caenorhabditis elegans slo-1 loss of function mutants. PLoS Pathog 7(4):e1001330. doi:10.1371/journal.ppat.1001330 PubMedCrossRefGoogle Scholar
  111. Williamson SM et al (2009) The nicotinic acetylcholine receptors of the parasitic nematode Ascaris suum: formation of two distinct drug targets by varying the relative expression levels of two subunits. PLoS Pathog 5(7):e1000517. doi:10.1371/journal.ppat.1000517 PubMedCrossRefGoogle Scholar
  112. Williamson SM, Walsh TK, Wolstenholme AJ (2007) The cys-loop ligand-gated ion channel gene family of Brugia malayi and Trichinella spiralis: a comparison with Caenorhabditis elegans. Invert Neurosci 7(4):219–226. doi:10.1007/s10158-007-0056-0 PubMedCrossRefGoogle Scholar
  113. Wolstenholme AJ (2011) Ion channels and receptor as targets for the control of parasitic nematodes. Int J Parasitol Drugs Drug Resist 1:2–13CrossRefGoogle Scholar
  114. Wu B et al (2009) The heme biosynthetic pathway of the obligate Wolbachia endosymbiont of Brugia malayi as a potential anti-filarial drug target. PLoS Negl Trop Dis 3(7):e475. doi:10.1371/journal.pntd.0000475 PubMedCrossRefGoogle Scholar
  115. Xu MJ et al (2010) RNAi-mediated silencing of a novel Ascaris suum gene expression in infective larvae. Parasitol Res 107(6):1499–1503. doi:10.1007/s00436-010-2027-3 PubMedCrossRefGoogle Scholar
  116. Yadav M, Singh A, Rathaur S, Liebau E (2010) Structural modeling and simulation studies of Brugia malayi glutathione-S-transferase with compounds exhibiting antifilarial activity: implications in drug targeting and designing. J Mol Graph Model 28(5):435–445. doi:10.1016/j.jmgm.2009.10.003 PubMedCrossRefGoogle Scholar
  117. Yang G et al (2006) Molecular cloning and characterization of a novel lactate dehydrogenase gene from Clonorchis sinensis. Parasitol Res 99(1):55–64. doi:10.1007/s00436-005-0125-4 PubMedCrossRefGoogle Scholar
  118. Yu Z et al (2011) Tirandamycins from Streptomyces sp. 17944 inhibiting the parasite Brugia malayi asparagine tRNA synthetase. Org Lett 13(8):2034–2037. doi:10.1021/ol200420u PubMedCrossRefGoogle Scholar
  119. Zhang L, Zhou XN (2008) Research progress on the action of praziquantel on voltage-gated Ca2+ channel in schistosomes. Zhongguo Ji Sheng Chong Xue Yu Ji Sheng Chong Bing Za Zhi 26(1):58–62PubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  1. 1.CSIR-Central Drug Research InstituteLucknowIndia

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