Analysis of fatty acid binding proteins (FABP) of parasitic cestodes as novel therapeutic targets

JULIAN A. BELGAMO; GISELA R. FRANCHINI; MATÍAS PÉREZ; MARA ROSENZVIT; JORGE L. PÓRFIDO; BETINA CÓRSICO

La Plata

Workshop; International workshop on drug desing and neglected tropical diseases; 2016

PurposeThe analysis of the genome and transcriptome of Echinococcus granulosus, E. multilocularis and Taenia solium suggests a high expression of lipid-binding proteins, including proteins that bind fatty acids (FABP), which participate in the uptake of host lipids modulating possibly the immune response. The aim of this work is to identify in the genome and characterize FABP from E. granulosus, E. multilocularis, causative species of hydatid disease, and T. solium, causing cysticercosis, to evaluate them as potential new targets for chemotherapy of these neglected diseases.MethodologyWe predicted five FABP isoforms in E. multilocularis, that were cloned and sequenced and are now being purified recombinantly for in vitro studies. In this project, we will complete the identification of the coding genes, clone and sequence the respective cDNAs of all the FABPs for each parasite. For the functional characterization we will measure ligand binding capacity and evaluate inhibitory compounds of this union. As a first approach, inhibitors of mammalian FABPs, will be tested as inhibitors of helmintic FABPs and this will assessed by fluorescence methodologies. Additionally, using an in vivo cysticercosis (T. crassiceps) model we will evaluate the effect of the pan FABP inhibitor (HTS01037) on T. crassiceps cisticerci.ResultsE. multilocularis, E. granulosus and T. solium present at least 5 isoforms of FABPs in their genomes. T. crassiceps express FABPs and hence it is possible to use this model to assess the effect of the inhibitor. Additionally, we observed a toxic effect of HTS01037 on cisticerci diminishing their viability and this would happen in a dose dependant manner.ConclusionAltogether, these results suggest that FABPs from cestodes (E. granulosus and T. solium) play important roles in the lipid metabolism of parasites and might be good therapeutic targets.