Inhibitor testing and identification of novel target genes in Fasciola hepatica
Infections of sheep and cattle with the liver fluke Fasciola hepatica cause enormous economical damage worldwide. Due to its zoonotic potential, also humans are affected with estimated 80 million infected people1. Mortality and morbitidiy is caused by migrating juvenile stages as well as liver-resident adult worm stages. The drug Triclabendazol is widely applied, often in mass treatment – however, already in the 1990s resistances occurred2. The development of novel fasciolid compounds with a broad activity against both fluke stages has therefore high priority. By tissue-specific transcriptomic approaches and knowledge transfer from our compound screening against Schistosoma mansoni (see project 6), we aim to identify fasciolidal substances as well as novel promising targets that are useful for future drug design.
|Fig. 1 Confocal microscopic images of juvenile Fasciola hepatica (carmine red staining). Whole fluke (left), oral sucker and „spine“-structure of tegument (center), ventral sucker and close-up of spines (right).|
Fig. 2 Tissue localization of transcripts of a new potential target gene (in situ hybridization on section of adult fluke).
1Mas-Coma S, Valero MA, Bargues MD. Fasciola, lymnaeids and human fascioliasis, with a global overview on disease transmission, epidemiology, evolutionary genetics, molecular epidemiology and control. Adv Parasitol 69:41–146. 2009
2Fairweather I. Triclabendazole progress report, 2005–2009: an advancement of learning? J. Helminthol 83:139–150. 2009