Initial studies of fatty acid binding proteins (FABP) from parasitic cestodes as novel therapeutic targets

BELGAMO J; ROSENZVIT M; FRANCHINI, G.R.; PORFIDO, J; BREHM K; RODRIGUEZ, S.; B. CÓRSICO

Congreso; Reunion anual Sociedad Arg. Biofisica; 2018

Echinococcus granulosus and Echinococcus multilocularis are the causative agentsof cystic and alveolar echinococcosis respectively, and are among the neglectedtropical diseases prioritized by the WHO. The scarcity of anthelmintic drugsavailable and the emergence of resistant parasites, makes the discovery of newanthelmintic drugs mandatory. The analysis of tapeworm genomes, showedabsence of genes for fatty acids and cholesterol de novo synthesis and highexpression of lipid binding proteins that could be involved in lipid acquisition fromhost tissues. Among them, fatty acid binding proteins (FABPs), small cytoplasmicproteins expressed in a tissue specific manner in mammmals, bind and transportfatty acids and retinoids, probably involved in signaling pathways trafficking andmembrane synthesis. In this work we are analysing the recombinant expressionand value of cestode? s FABPs as novel drug targets. In silico analysis of tapewormgenomes revealed the existence of at least five FABP coding genes in the genomesof E. granulosus, E. multilocularis and T. solium. The sequences from E.multilocularis FABPs were cloned, sequenced and compared with the informationavailable at the databases. Analysis of expression shows that E. multilocularisFABPs? seem to be transcribed in a stage-specific manner. The isoforms tested forbinding show that they bind fatty acids with an affinity comparable to themammalian counterparts. An inhibitor of mammalian FABPs (HTS01037) wastested in vitro on some isoforms employing fluorescence based methodologies.Additionally, using an in vivo cysticercosis (T. crassiceps) model the effect of theFABP inhibitor was evaluated on T. crassiceps cisticerci. Preliminary results indicatethat HTS01037 presents a strong effect on parasite viability. Altogether, theseresults suggest that FABP isoforms may play specific roles in different stages/tissues, related to lipid metabolism of parasites and might be good therapeutictargets.