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

KLAUS BREHM; GISELA R. FRANCHINI; JORGE L. PÓRFIDO; BETINA CÓRSICO; JULIAN A. BELGAMO; MARA ROSENZVIT

Cape Cod

Congreso; Molecular Helminthology: An Integrated Approach.; 2017

Introduction The focus of our work centers on the analysis of new therapeutic targets for the control of neglected diseases caused by cestodes. The analysis of tapeworm genomes (E. granulosus, E. multilocularis and T. solium) indicates the existence of various genes coding for fatty acid binding proteins (FABPs). These proteins may participate in the uptake of host lipids and modulation of the immune response. Cestode?s FABPs are highly divergent from the host counterparts and may exert essential functions, thus fulfilling the main requirements for good selective therapeutic targets. We propose to evaluate FABPs as new drug targets for alveolar and cystic echinococcosis, and cysticercosis.Methods In silico analysis of tapeworm genomes was performed in order to identify the FABPs? coding genes for E. granulosus, E. multilocularis and T. solium. The sequences were cloned, sequenced and compared with the information available at the databases. Analysis of expression was performed employing RT-PCR and Western blot. For the functional characterization of the proteins, ligand binding capacity was measured and, as a first approach, an inhibitor of mammalian FABPs (HTS01037) was tested employing fluorescence methodologies. Additionally, using an in vivo cysticercosis (T. crassiceps) model the effect of the FABP inhibitor was evaluated on T. crassiceps cisticerci.Results E. multilocularis, E. granulosus and T. solium present at least 5 isoforms of FABPs in their genomes. E. multilocularis FABPs? seem to be transcribed in a stage-specific manner (Figure 1). One of the isoforms tested for binding shows that it binds fatty acids with an affinity comparable to the mammalian counterparts. Preliminary results indicate that HTS01037 presents a strong effect on parasite viability (Figure 2). Discussion 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.