Identification of putative markers of triclabendazole resistance by a genome-wide analysis of genetically recombinant Fasciola hepatica

Abstract

Despite years of investigation into triclabendazole (TCBZ) resistance in Fasciola hepatica, the genetic mechanisms responsible remain unknown. Extensive analysis of multiple triclabendazole-susceptible and -resistant isolates using a combination of experimental in vivo and in vitro approaches has been carried out, yet few, if any, genes have been demonstrated experimentally to be associated with resistance phenotypes in the field. In this review we summarize the current understanding of TCBZ resistance from the approaches employed to date. We report the current genomic and genetic resources for F. hepatica that are available to facilitate novel functional genomics and genetic experiments for this parasite in the future. Finally, we describe our own non-biased approach to mapping the major genetic loci involved in conferring TCBZ resistance in F. hepatica.

TGF-β superfamily members from the helminth Fasciola hepatica show intrinsic effects on viability and development

“…Identification of putative TGF-β superfamily members of F. hepatica was carried out by tBlastn searching of an unpublished genome database [19] using TGF-β protein sequences from closely related mammalian hosts of F. hepatica and the closely related helminth parasite, S. mansoni . The tBlastn search returned 4 hits for each of the B. taurus and S. mansoni queries; the top 3 hits originated from the same scaffolds numbered 40128, 30949 and 35064 (Additional file 1).…”

“…Genome analysis was conducted using the putative F. hepatica genome produced in the laboratory of Dr Jane Hodgkinson University of Liverpool [19]. TGF-β like sequences were identified in the F. hepatica genome through a tBlastn search of the draft genome contigs using protein sequences of TGF-β1-3 from mammalian hosts and SmInAct, a TGF-β like protein from S. mansoni as queries.…”

The T687G SNP in a P-glycoprotein gene of Fasciola hepatica is not associated with resistance to triclabendazole in two resistant Australian populations

“…More work is needed to determine if genetic variation in the Pgp gene(s) do in fact influence TCBZ efficacy. The analysis of genome-wide markers that segregate with resistance in a genetic cross of TCBZ susceptible and resistant flukes may assist with the identification of regions of the genome under selection and, in turn, the mechanism(s) of TCBZ resistance [21].…”

Identification of Fasciola spp. in the East of Iran, Based on the Spermatogenesis and Nuclear Ribosomal DNA (ITS1) and Mitochondrial (ND1) Genes

“…One of the main problems in anthelmintic resistance of this parasite is due to aspects of biology and population structure and pathogenicity, and the control of fascioliasis depends on genetic diversity (10,11). Both of these species may be identified by applying DNA sequences of nuclear ribosomal DNA internal transcribed spacers (ITS), and sequences of CO1 and ND1 as mitochondrial genes to analyze intraspecific phylogenetic relationship of Fasciola spp.…”