Fatty acid binding proteins (FABP) of parasitic cestodes: functional studies and evaluation as novel therapeutic targets

JULIAN A. BELGAMO; URIEL KOZIOL; ESTELA CASTILLO; MATÍAS PÉREZ; MARA ROSENZVIT; BETINA CÓRSICO; GISELA R. FRANCHINI; JORGE L. PÓRFIDO; MICHAELA HERZ; KLAUS BREHM

Hydra

Congreso; Molecular and Cellular Biology of Helminths IX; 2018

The analysis of the genome and transcriptome of Echinococcus granulosus and E. multilocularis, causative agents of hydatid disease, suggests a high expression of lipid-binding proteins, including proteins that bind fatty acids (FABPs), which may participate in the uptake of host lipids for energy metabolism, membrane construction, and lipid-based signalling, the latter possibly also encompassing modification of the host?s immune and inflammatory defence systems. The aim of this work is to identify FABPs in the genome of E. granulosus and E. multilocularis, characterise their function and to evaluate them as potential new targets for chemotherapy. We predicted five FABP isoforms in E. multilocularis, that were cloned and sequenced and are now being purified recombinantly for in vitro studies. The isoforms tested for ligand binding show an affinity comparable to the mammalian counterparts. In addition, transcriptomic data from several sources showed differential expression patterns of FABPs at different stages of the life cycle of E. multilocularis being EmFABP1 the most highly expressed FABP in this organism. Whole mount in situ hybridization samples also revealed that EmFABP1 is present in tegumental cells from vesicles and from the distal part of protoscoleces. In this sense other EmFABPs are under study. Regarding, the analysis of cestode FABPs as novel therapeutic targets, in vitro binding of an inhibitor of mammalian FABPs (HTS01037) was assessed by fluorescence methodologies. Preliminary results indicate that HTS01037 binds to cestode FABPs with lower affinities than mammalian. Additionally, using an in vivo cysticercosis (T. crassiceps) model we evaluated the effect of HTS01037 on T. crassiceps cisticerci. Altogether, these results suggest that FABP isoforms may play specific roles in different stages/tissues, related to lipid metabolism of parasites and might be good therapeutic targets.