A single amino acid substitution in isozyme GST mu in Triclabendazole resistant Fasciola hepatica (Sligo strain) can substantially influence the manifestation of anthelmintic resistance

Fernández, Vanesa; Estein, Silvia Marcela; Ortiz, Pedro; Luchessi, P.; Solana, Victoria; Solana, H.

doi:10.1016/j.exppara.2015.10.007

Cited by 17 publications

(7 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A role for mutations in one Pgp gene in TCBZ-R was proposed but the few mutations that have been described [61] appear to be more related to variation between strains and isolates of F. hepatica than a true TCBZ-R phenotype since these mutations were not associated with resistance in Australian or Scottish TCBZ-resistant isolates [62,63]. A single amino acid substitution in glutathione S-transferase (GST) has been implicated in a TCBZ-resistant fluke isolate, but this has not yet been confirmed in any other TCBZ-resistant isolates [64]. An analysis of the total soluble proteome of TCBZ-resistant and susceptible flukes was also performed, with and without exposure to TCBZ-SO, to search for key differences in the protein response to TCBZ exposure in adult flukes [65].…”

Section: Mechanism(s) Of Tcbz-rmentioning

confidence: 99%

Current Threat of Triclabendazole Resistance in Fasciola hepatica

Kelley

Elliott

Beddoe

et al. 2016

Trends in Parasitology

252

185

View full text Add to dashboard Cite

Triclabendazole (TCBZ) is the only chemical that kills early immature and adult Fasciola hepatica (liver fluke) but widespread resistance to the drug greatly compromises fluke control in livestock and humans. The mode of action of TCBZ and mechanism(s) underlying parasite resistance to the drug are not known. Due to the high prevalence of TCBZ resistance (TCBZ-R), effective management of drug resistance is now critical for sustainable livestock production. Here, we discuss the current status of TCBZ-R in F. hepatica, the global distribution of resistance observed in livestock, the possible mechanism(s) of drug action, the proposed mechanisms and genetic basis of resistance, and the prospects for future control of liver fluke infections using an integrated parasite management (IPM) approach.

show abstract

Section: Mechanism(s) Of Tcbz-rmentioning

confidence: 99%

Current Threat of Triclabendazole Resistance in Fasciola hepatica

Kelley

Elliott

Beddoe

et al. 2016

Trends in Parasitology

252

185

View full text Add to dashboard Cite

show abstract

“…Moreover, the parasites thrive in such an environment by adjusting their metabolism and varying protein expression. For example, the resistance of certain F. hepatica isolates to the drug salicylanilide has been linked to increased expression of FhGST [ 250 ], and an amino acid substitution in position 143 of the GST was shown to increase TCBZ susceptibility of isolates [ 251 ].…”

Section: Mechanisms Of Pathogenicity Of Fasciola Spp Parasitesmentioning

confidence: 99%

Pathogenicity and virulence of the liver flukesFasciola hepaticaandFasciolaGiganticathat cause the zoonosis Fasciolosis

et al. 2021

View full text Add to dashboard Cite

Fasciolosis caused by the liver flukes Fasciola hepatica and Fasciola gigantica is one of the most important neglected parasitic diseases of humans and animals. The ability of the parasites to infect and multiply in their intermediate snail hosts, and their adaptation to a wide variety of mammalian definitive hosts contribute to their high transmissibility and distribution. Within the mammalian host, the trauma caused by the immature flukes burrowing through the liver parenchyma is associated with most of the pathogenesis. Similarly, the feeding activity and the physical presence of large flukes in the bile ducts can lead to anemia, inflammation, obstruction and cholangitis. The high frequency of non-synonymous polymorphisms found in Fasciola spp. genes allows for adaptation and invasion of a broad range of hosts. This is also facilitated by parasite’s excretory-secretory (ES) molecules that mediate physiological changes that allows their establishment within the host. ES contains cathepsin peptidases that aid parasite invasion by degrading collagen and fibronectin. In the bile ducts, cathepsin-L is critical to hemoglobin digestion during feeding activities. Other molecules (peroxiredoxin, cathepsin-L and Kunitz-type inhibitor) stimulate a strong immune response polarized toward a Treg/Th2 phenotype that favors fluke’s survival. Helminth defense molecule, fatty acid binding proteins, Fasciola -specific glycans and miRNAs modulate host pro-inflammatory responses, while antioxidant scavenger enzymes work in an orchestrated way to deter host oxidant-mediated damage. Combining these strategies Fasciola spp. survive for decades within their mammalian host, where they reproduce and spread to become one of the most widespread zoonotic worm parasites in the world.

show abstract

“…Studies of morphological and metabolic differences between susceptible and resistant strains has been reported, based on comparison of the first available well-characterized isolates of European origin (Mottier et al , 2006; Solana et al , 2009; Ceballos et al , 2010; Hanna et al , 2010; Scarcella et al , 2011, 2012; reviewed in Kelley et al , 2016). The search for mutations in putative target (tubulin) or effector (P-glycoprotein (PGP), glutathione S-transferase (GST)) genes has been based on European isolates (Ryan et al , 2008; Wilkinson et al , 2012; Fernández et al , 2015), but confirmation in other isolates is needed. In fact, the PGP point mutation proposed as being associated with resistant isolates was not found to be associated with Australian isolates (Elliott & Spithill, 2014), and studies under way on some of the South American isolates have not found the variant to be associated with resistance (Solana and Tort, unpublished).…”

Section: Control Approachesmentioning

confidence: 99%

Fasciolosis in South America: epidemiology and control challenges

Carmona

Tort

2016

J. Helminthol.

View full text Add to dashboard Cite

Fasciolosis caused by Fasciola hepatica severely affects the efficiency of livestock production systems worldwide. In addition to the economic impact inflicted on livestock farmers, fasciolosis is an emergent zoonosis. This review emphasizes different aspects of the disease in South America. Available data on epidemiology in bovines and ovines in different countries, as well as a growing body of information on other domestic and wildlife definitive hosts, are summarized. The issue of drug resistance that compromises the long-term sustainability of current pharmacological strategies is examined from a regional perspective. Finally, efforts to develop a single-antigen recombinant vaccine in ruminants are reviewed, focusing on the cases of leucine aminopeptidase or thioredoxin glutathione reductase.

show abstract

A single amino acid substitution in isozyme GST mu in Triclabendazole resistant Fasciola hepatica (Sligo strain) can substantially influence the manifestation of anthelmintic resistance

Cited by 17 publications

References 25 publications

Current Threat of Triclabendazole Resistance in Fasciola hepatica

Current Threat of Triclabendazole Resistance in Fasciola hepatica

Pathogenicity and virulence of the liver flukesFasciola hepaticaandFasciolaGiganticathat cause the zoonosis Fasciolosis

Fasciolosis in South America: epidemiology and control challenges

Contact Info

Product

Resources

About