Environmental circulation of the anthelmintic drug albendazole affects expression and activity of resistance-related genes in the parasitic nematode Haemonchus contortus

The induction and inhibition of UDP-glycosyltransferases in Haemonchus contortus and their role in the metabolism of albendazole

“…Not many UGTs were upregulated by ABZ nor ABZSO after 4-h exposure both in the males and females, with more transcripts upregulated in males after 12 h. Similarly, the 4-h exposure to ABZ did not lead to any induction of UGTs in the juvenile stages ( Kellerova et al, 2020a ), a result also found with ABZ in very high concentrations in H. contortus adults ( Stasiuk et al, 2019 ). On the other hand, the exposure of H. contortus adults to sub-lethal concentrations of ABZ and ABZSO (1 μM and lower) for 4 and 12 h ex vivo ( Kellerova et al, 2020b ), and for several weeks in vivo ( Dimunová et al, 2022 ) led to the transcriptional response of several UGTs ( Table 4 ). The upregulation of UGT368A1 after 4-h exposure to 10 μM ABZ observed in present study in H. contortus adults has also previously been found in H. contortus larvae L3 ( Kellerova et al, 2020a ).…”

“…UGTs induced more than two fold are displayed in bold. Treatment Females Males References sub-lethal ABZ (4 h/12h) UGT365A1 UGT367A1 UGT368B2 UGT10B1 UGT26A2 Kellerova et al (2020b) UGT365A1 UGT365B1 UGT365B3 UGT365B5 UGT366C1 UGT368A2 UGT368B2 UGT371A1 sub-lethal ABZSO (4 h/12h) UGT10B1 UGT24D1 UGT24D2 UGT366A1 UGT366C1 UGT372A1 UGT24C1 Kellerova et al (2020b) UGT26A2 UGT365B5 UGT366C1 UGT368B1 UGT369A1 UGT371A1 UGT372A1 ABZ in vivo UGT365B1 UGT365B5 UGT366B1/B2 UGT368B2 UGT24B1 Dimunová et al (2022) UGT24C1 UGT26A2 UGT365B1 UGT365B5 UGT368A1 UGT368A2 UGT368B2 UGT370B1 10 μM ABZ (4 h/12h) UGT368A1 UGT367A1 a UGT365B3 10 μM ABZSO (4 h/12h) UGT10B1 UGT368B2 UGT26A2 …”

“…In the free-living nematode Caenorhabditis elegans, the nonsense point mutation of ugt-22 , which catalyses deactivation of anthelmintic albendazole (ABZ), increased the efficacy of ABZ ( Fontaine and Choe, 2018 ). In addition, the contact of the H. contortus adults with sub-lethal doses of ABZ (1 μM and lower) leads to the induction of several UGTs, and subsequently to improved ABZ deactivation due to a higher production of inactive glucosides ( Kellerova et al, 2020b ; Dimunová et al, 2022 ). Phenobarbital (PHB), a classical inducer of UGTs and other XMEs, increased metabolism of anthelmintic naphthalophos in H. contortus larvae ( Kotze et al, 2014 ); nothing is known, however, about the effect of PHB on ABZ metabolism in H. contortus.…”

Histidine acid phosphatase domain-containing protein from Haemonchus contortus is a stimulatory antigen for the Th1 immune response of goat PBMCs

“…In livestock, parasite control is currently accomplished using three major classes of anthelmintics: benzimidazoles, macrolides and imidazothiazoles [ 1 , 3 ]. However, excessive use of anthelmintics in domestic animals can lead to nematode resistance [ 3 , 4 ], and the emergence of multi-drug-resistant nematodes poses a potential threat to public health [ 5 – 10 ]. To develop an effective vaccine, it is imperative to understand the mechanisms of host-nematode interactions, particularly how nematode antigenic molecules modulate the host immune system.…”

The Prevalence of Trichinella spiralis in Domestic Pigs in China: A Systematic Review and Meta-Analysis

“…Currently, as a result of drug-resistance escalation and immune failure [ 20 , 21 , 22 , 23 ], pig industries have to alter approaches to controlling the parasitic nematodes by developing new vaccines or drugs against T. spiralis infection in pigs. The lack of information on the epidemiology also lead to difficulty in the development of new vaccines, drugs, and the diagnosis technology of trichinellosis.…”