Histone deacetylase enzymes of cestode parasites, characterization as potential drug targets of neglected diseases

CELENTANO, ANA M.; ROSENZVIT, MARA C.; TOSCANINI, AGUSTINA; NUSBLAT, ALEJANDRO; VACA, HUGO R.; CUESTAS, MARÍA LUJÁN

CABA

Congreso; Drug Discovery for Neglected Diseases International Congress 2018. 4th Scientific Meeting of Research Network Natural Products against Neglected Diseases; 2018

Facultad de Bioquímica y Farmacia, UBA

Echinococcosis is a disease caused by the cestode parasite Echinococcus granulosus. This disease represents asignificant problem in human and animal health and is considered neglected and a priority matter for the WHO [1].Currently, albenzadole is the only drug licensed available in Argentina for treatment. Therefore, it is very important toidentify new alternative drugs against these parasites. Epigenetic mechanisms play an important role in the chromatinstructure and, consequently, in regulation of gene expression and other cellular processes. Specifically, histonedeacetylase enzymes (HDACs) have been validated as drug targets for the treatment of cancer and other diseases,including parasitic infections [2,3]. Our aim is to study the epigenetic mechanisms used by these helminths that maybe suited for chemotherapy intervention. In this work we characterize cestode HDACs as possible drug targets. First,we performed a homology search for HDAC on cestode genomes available on WormBaseParasite databank [4]. HDACdomains were identified in putative sequences and gene expression was confirmed by RNAseq data. The pan HDACsinhibitor ?Trichostatin A? (TSA) was used in Mesocestoides corti tetrathyridia (TTy), a cestode laboratory model.Viability, motility and morphology alterations of TSA-treated TTy were measured as well as the effect on parasitehistone H4 acetylation and pan-acetylaled proteins by inmunoblot assay. HDAC genes of class I and II were foundon cestodes genomes. All genes are expressed in different parasite stages of the Genus Echinococcus, being HDAC1and HDAC8 differentially expressed in metacestode, the clinical relevant stage for human. TSA decreased by 40% theviability of TTy after 6 days treatment (P