CONICET | Buscador de Institutos y Recursos Humanos

Echinococcus granulosus and Echinococcus multilocularis are the causative agents of cystic and alveolar echinococcosis respectively, and are among the neglected tropical diseases prioritized by the WHO. The scarcity of anthelmintic drugs available and the emergence of resistant parasites, makes the discovery of new anthelmintic drugs mandatory. The analysis of tapeworm genomes, showed absence of genes for fatty acids and cholesterol de novo synthesis and high expression of lipid binding proteins that could be involved in lipid acquisition from host tissues. Among them, fatty acid binding proteins (FABPs), small cytoplasmic proteins expressed in a tissue specific manner in mammmals, bind and transport fatty acids and retinoids, probably involved in signaling pathways trafficking and membrane synthesis. In this work we are analysing the recombinant expression and value of cestode? s FABPs as novel drug targets. In silico analysis of tapeworm genomes revealed the existence of at least five FABP coding genes in the genomes of E. granulosus, E. multilocularis and T. solium. The sequences from E. multilocularis FABPs were cloned, sequenced and compared with the information available at the databases. Analysis of expression shows that E. multilocularis FABPs? seem to be transcribed in a stage-specific manner. The isoforms tested for binding show that they bind fatty acids with an affinity comparable to the mammalian counterparts. An inhibitor of mammalian FABPs (HTS01037) was tested in vitro on some isoforms employing fluorescence based methodologies. Additionally, using an in vivo cysticercosis (T. crassiceps) model the effect of the FABP inhibitor was evaluated on T. crassiceps cisticerci. Preliminary results indicate that HTS01037 presents a strong effect on parasite viability. 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.