CHARACTERIZATION OF HISTONE DEACETYLASE ENZYMES OF CESTODE PARASITES AS POTENTIAL DRUG TARGETS OF NEGLECTED DISEASES

VACA H; CAMICIA F; CUCHER M; KAMENETZKY L; MACCHIAROLI N; CELENTANO A; ROSENZVIT M

Congreso; Reunión Conjunta de Sociedades de Biociencias; 2017

Cestode parasites cause neglected diseases such as hydatidosis. These parasites have complex life cycles undergoing metamorphic events that comprise cell proliferation, differentiation and death. This suggests the involvement of a complex system of gene expression control that has been associated with changes in chromatin struc ture in trematode parasites. Histone deacetylase enzymes (HDAC) remove acetyl groups from histones and other cellular effectors, thus directly influencing the chromatin structure and thereby regulating gene transcription and other cellular processes. HDAC have been validated as drug targets for the treatment of cancer and other diseases including parasitic infections. However, knowledge of HDAC in cestode parasites is lacking. Previously, we have shown the presence and transcription of HDAC genes in several species of cestode parasites. In this work, we aimed to study the effect of the pan-HDAC inhibitor Trichostatin A (TSA) in Mesocestoides corti, a cestode laboratory model. We found a decrease in the viability, measured by AlamarBlue assay and motility index determination, and observed phenotypic alterations in M. corti larvae upon incubation with TSA. To assess the molecular target of TSA, we evaluated changes in the total amount of acetylated histone H4 by western blot using anti-acetylated histone H4 antibody. We observed a band corresponding to acetylated H4 histone in parasites treated with TSA but not in control parasites, suggesting that TSA strongly inhibits H4 histone deacetylation. This effect was not observed in parasites treated with praziquantel and albendazole suggesting a specific effect of TSA. These findings suggest that HDAC could have an essential role in cestode development and survival. This work provides a first step into the study of epigenetic mechanisms in cestode parasites and explores new alternatives to treat the diseases they cause.