Abstract
The nematode Haemonchus contortus, a gastrointestinal parasite of ruminants, can severely burden livestock production. Although anthelmintics are the mainstay in the treatment of haemonchosis, their efficacy diminishes due to drug-resistance development in H. contortus. An increased anthelmintics inactivation via biotransformation belongs to a significant drug-resistance mechanism in H. contortus. UDP-glycosyltransferases (UGTs) participate in the metabolic inactivation of anthelmintics and other xenobiotic substrates through their conjugation with activated sugar, which drives the elimination of the xenobiotics due to enhanced solubility. The UGTs family, in terms of the biotransformation of commonly used anthelmintics, has been well described in adults as a target stage. In contrast, the free-living juvenile stages of H. contortus have attracted less attention. The expression of UGTs considerably varies throughout the life cycle of the juvenile nematodes, suggesting their different roles. Furthermore, the constitutive expression in a susceptible strain with two resistant strains shows several resistance-related changes in UGTs expression, and the exposure of juvenile stages of H. contortus to albendazole (ABZ) and ABZ-sulfoxide (ABZSO; in sublethal concentrations) leads to the increased expression of several UGTs. The anthelmintic drug ABZ and its primary metabolite ABZSO biotransformation, tested in the juvenile stages, shows significant differences between susceptible and resistant strain. Moreover, higher amounts of glycosidated metabolites of ABZ are formed in the resistant strain. Our results show similarly, as in adults, the UGTs and glycosidations significant for resistance-related differences in ABZ biotransformation and warrant further investigation in their individual functions.
Highlights
The nematode Haemonchus contortus is a problematic and highly successful parasite of small ruminants
We explored the inducibility of UGTs by ABZ and ABZSO in H. contortus juvenile stages
The nematode eggs were collected by differential sieving through three stacked sieves as described by Varady et al (2007) and recovered with a sucrose flotation technique followed by washing in tap water
Summary
The nematode Haemonchus contortus is a problematic and highly successful parasite of small ruminants. Several other drug-resistance mechanisms in H. contortus have been described, with one of these based on increased deactivation and/or efflux of anthelmintics via the increased expression of drug-metabolizing enzymes. Glycosidation or conjugation of activated sugar to a lipophilic compound, in general, is performed by UDP-glycosyltransferases (UGTs), during the second phase of biotransformation, causing the metabolic inactivation of xenobiotic substrates. Such a conjugation drives the elimination of the compound due to enhanced solubility. If the treated animal is left freely on pasture, the juvenile stages can get into contact with the drug, which may contribute to resistance development. We explored the inducibility of UGTs by ABZ and ABZSO in H. contortus juvenile stages
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