Evento IV Seminario Internacional de Sanidad Agropecuaria starts on 8 de mayo de 2023, 8:00:00 -0400
MOLECULAR BASIS OF PHARMACORRESISTANCE TO BENZIMIDAZOLS IN β-TUBULIN MUTANTS OF CYATHOSTOMINS
(1 hora 30 minutos)

MOLECULAR BASIS OF PHARMACORRESISTANCE TO BENZIMIDAZOLS IN β-TUBULIN MUTANTS OF CYATHOSTOMINS
Dany Naranjo Feliciano Researcher  at Centro Nacional de Sanidad Agropecuaria danynaranjofeliciano@gmail.com



Cyathostomins are highly prevalent equine gastrointestinal parasites. Benzimidazole-2-carbamate derivatives, such as albendazol and oxibendazol, are the most commonly used drugs for the control and treatment in Cuba. These antiparasitics selectively bind to the β-tubulin monomer and inhibit microtubule polymerization. However β-tubulin mutations can convert susceptible wild type worms to unsusceptible, thereby enabling benzimidazole resistance. Moreover, the relation between the mechanism of action and the binding site of bezimidazole has not yet been explained accurately. By using the β-tubulin gene DNA fragment sequence - Cylicostephanus goldi (wild type control, not determined) - and five cyathostomin species (Cyathostomum catinatum, Cyathostomum pateratum, Cylicostephanus longibursatus, Cylicostephanus minutus, Cylicocyclus nassatus) pre-selected by extra-label use of albendazole and resistant to oxibendazole, were employed as initial biological material. By applying homology modeling techniques, we were able to build a 3D structure of the β-tubuline protein, generated using the structure of the mammal Ovis aries, considered as a low susceptible organism, as a template. In order to identify at the molecular level, of the mode of action, molecular docking and molecular dynamics calculations were carried out with these models. The results were in good agreement with the most common amino acid mutations associated with drug resistance (with single -F167Y- and doubly mutant -S165C, F167Y-) in the colchicine binding site to β-tubulin. This study provided insight into the structural composition of β-tubulin and microtubule in cyathostomins and possible mechanisms of benzimidazole resistance within the study population.
3CE (Parque Científico Tecnológico de La Habana S.A.) Oro
Mipyme Lácteos Rojas SURL (Producción de Alimentos (productos Lácteos)) Oro
Mipyme AlaSoluciones (Fabricación de equipos de medición, prueba, navegación y control) Plata
Sociedad Mercantil Empresa de Ciencia y Tecnología de Interfaz del Complejo Científico Docente Productivo de Mayabeque Bronce
Programa Sectorial de Sanidad Animal y Vegetal
Organización Panamericana de la Salud