Pleiotropic alterations in gene expression in Latin American Fasciola hepatica isolates with different susceptibility to drugs

Abstract

BackgroundFasciola hepatica is the main agent of fasciolosis, a zoonotic disease affecting livestock worldwide, and an emerging food-borne disease in humans. Even when effective treatments are available, drugs are costly and can result in tolerance, liver damage and normally they do not prevent reinfection. Drug-resistant strains in livestock have been reported in various countries and, more worryingly, drug resistance in human cases has emerged in South America. The present study aims to characterize the transcriptome of two South American resistant isolates, the Cajamarca isolate from Peru, resistant to both triclabendazole and albendazole (TCBZR/ABZR) and the Rubino isolate from Uruguay, resistant to ABZ (TCBZS/ABZR), and compare them to a sensitive strain (Cenapa, Mexico, TCBZS/ABZS) to reveal putative molecular mechanisms leading to drug resistance.ResultsWe observed a major reduction in transcription in the Cajamarca TCBZR/ABZR isolate in comparison to the other isolates. While most of the differentially expressed genes are still unannotated, several trends could be detected. Specific reduction in the expression levels of cytoskeleton proteins was consistent with a role of tubulins as putative targets of triclabendazole (TCBZ). A marked reduction of adenylate cyclase might be underlying pleiotropic effects on diverse metabolic pathways of the parasite. Upregulation of GST mu isoforms suggests this detoxifying mechanism as one of the strategies associated with resistance.ConclusionsOur results stress the value of transcriptomic approaches as a means of providing novel insights to advance the understanding of drug mode of action and drug resistance. The results provide evidence for pleiotropic variations in drug-resistant isolates consistent with early observations of TCBZ and ABZ effects and recent proteomic findings.Electronic supplementary materialThe online version of this article (10.1186/s13071-017-2553-2) contains supplementary material, which is available to authorized users.

Eurytrema coelomaticum: updated morphology of adult worms using advanced microscopy experiments

“…In recent years, increasing drug resistance worldwide has been observed in gastrointestinal helminths that parasitize livestock (Radio et al ., 2018). Hence, strategies are necessary to develop and test new and effective anthelmintic drugs (Srivastava & Misra-Bhattacharya, 2015).…”

Different SNPs in Fasciola hepatica P-glycoprotein from diverse Latin American populations are not associated with Triclabendazole resistance

“…While these results compromise the causal role of the previously indicated SNP, they do not exclude PGP as a candidate to resistance. Indeed, the region studied so far represent less than a tenth of the original protein, and our transcriptomic evidence [16] show that much variation exist along the 42 kb of the gene. Furthermore, the genomic sequences of [17] with the CLC Genomics Workbench package (Qiagen, Aarhus A/S) as described [16].…”

Reference gene analysis and its use for kinase expression profiling in Fasciola hepatica

“…The ortholog of a glutamyl-prolyl-tRNA synthetase ( eprs ) was included based on its stable expression in different strains of F . hepatica 19 . Finally, for comparison, we included the well-known housekeeping gene gapdh , which is currently widely used for normalisation also in F .…”