CIVETAN   23983
CENTRO DE INVESTIGACION VETERINARIA DE TANDIL
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Analysis of P-glycoprotein gene transcripts in Fasciola hepatica and its relation with resistance to triclabendazole
Autor/es:
SOLANA M.V.; SOLANA H.; SCARCELLA S.; ORTIZ OBLITAS P.; TORT J.
Lugar:
Liverpool
Reunión:
Conferencia; 25 th International Conference - WAAVP2015; 2015
Institución organizadora:
the World Association for the Advancement of Veterinary Parasitology.
Resumen:
Fasciolosis is a parasitic disease caused by the
trematodeFasciola hepatica. Itscontrol is mainly basedon the use of triclabendazole
(TCBZ), a halogenated benzimidazolewith excellent efficacy against juvenile and
adult stages. Resistance to TCBZ in F. hepaticahas
been reported in many parts of the world.Benzimidazole resistance in nematodes
is mainly caused by specific amino acid substitutions in β-tubulin resulting
from a nucleotide substitution in the gene. However, the resistance to TCBZ in F. hepaticais not associated with
changes in this molecule.The
increased cellular efflux of TCBZ in F.
hepaticais relatedto P-glycoproteins(PGP) and a T687G single nucleotide polymorphism
(SNP) was initially suggested as responsible for the resistant phenotype. In
the present work, a complete PGP sequence has been assembled based on sequences
available in databases. We analyzed transcriptsfrom this gene region in TCBZ resistant
strains from Peru and Argentina andin susceptiblestrains from Mexico and
Ireland. We observed that the T687G SNP is not associated with resistance to
TCBZ. Instead, we identified other SNPs, including variants in the coding
region and in introns. Two SNPs A617T and T267G, which fall in a PGP intron,are
shared by all resistant strains but also are present in some susceptible ones. RT-PCR
from adult RNA showed no evidence of alternative splicing. Our results
highlight the lack of clear association of SNPs in this PGP gene with resistanceto TCBZ. The recent release of two assemblies
of the F.hepatica genome revealing
the presence of multiple ABC transporters and multidrug resistance genes opens
new avenues for investigating variants associated with the resistance of F. hepatica to TCBZ.