IMPAM   23988
INSTITUTO DE INVESTIGACIONES EN MICROBIOLOGIA Y PARASITOLOGIA MEDICA
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
NEW POTENTIAL DRUG TARGETS OF NEGLECTED DISEASES PRODUCED BY CESTODE PARASITES: HISTONE DEACETYLASES ENZYMES
Autor/es:
FEDERICO CAMICIA; LAURA KAMENETZKY; HUGO VACA; NATALIA MACCHIAROLI; MARA C. ROSENZVIT; LUCAS MALDONADO; MARCELA ALEJANDRA CUCHER
Lugar:
Mar del Plata, Provincia de Buenos Aires
Reunión:
Congreso; LXI Reunión Anual de la Sociedad Argentina de Investigación Clínica; 2016
Institución organizadora:
Sociedad Argentina de Investigacion Clinica SAIC
Resumen:
Cystic hydatidosis and cysticercosis, caused by the cestode parasites Echinococcus granulosus and Taenia solium respectively, are considered neglected diseases and a priority for de WHO. These zoonoses represent significant problems in human and animal health in South America. Because the only drugs available for the treatment are albenzadole and praziquantel and the possible emergence of resistant parasites, it is very important to identify new drugs against these parasites. The cestode parasites have complex life cycles and show a remarkable phenotypic plasticity that involves a complex system of control of gene expression that is associated in trematodes which changes in chromatin structure. In this work we propose to study epigenetic mechanism in cestodes parasites, principally the histone deacetylase enzyme (HDAC) as a target of drugs for parasitic diseases. Bioinformatic analyses performed in recently available cestode genomes (Tsai et al, 2013; Maldonado et al, submitted) showed that HDACs are present in Echinococcus granulosus sensu stricto G1, Echinococcus canadensis G7, Echinococcus multilocularis, T. solium and Mesocestoides corti. In addition, growth of M. corti (model of cestodes parasites) in the presence of generic HDAC inhibitor showed a decrease in viability, measured by alamar blue reduction, and phenotypic alterations compared with untreated parasites. DNA amplifications performed by RT-PCR resulted in PCR products that were cloned and characterized by sequence analyses as HDAC8s in E. canadensis and M. corti. The sequence conservation of these enzymes with the homologs in the trematode Schistosoma mansoni suggests that the drugs designed against S. mansoni HDACs could be effective against cestodes. This is currently being tested in our lab..The characterization of HDACs in cestodes will help to understand the particular development features of parasite cestodes and provide new candidate therapeutic targets against neglected parasitic diseases.