UDP-glycosyltransferase family in Haemonchus contortus: Phylogenetic analysis, constitutive expression, sex-differences and resistance-related differences

Matoušková, P. et al. (2018) UDP-glycosyltransferase family in Haemonchus contortus: Phylogenetic analysis, constitutive expression, sex-differences and resistance-related differences. International Journal for Parasitology: Drugs and Drug Resistance, 8(3), pp. 420-429. (doi: 10.1016/j.ijpddr.2018.09.005) (PMID:30293057) (PMCID:PMC6174829)

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Abstract

UDP-glycosyltransferases (UGT), catalysing conjugation of UDP-activated sugar donors to small lipophilic chemicals, are widespread in living organisms from bacteria to fungi, plant, or animals. The progress of genome sequencing has enabled an assessment of the UGT multigene family in Haemonchus contortus (family Trichostrongylidae, Nematoda), a hematophagous gastrointestinal parasite of small ruminants. Here we report 32 putative UGT genes divided into 15 UGT families. Phylogenetic analysis in comparison with UGTs from Caenorhabditis elegans, a free-living model nematode, revealed several single member homologues, a lack of the dramatic gene expansion seen in C. elegans, but also several families (UGT365, UGT366, UGT368) expanded in H. contortus only. The assessment of constitutive UGT mRNA expression in H. contortus adults identified significant differences between females and males. In addition, we compared the expression of selected UGTs in the drug-sensitive ISE strain to two benzimidazole-resistant strains, IRE and WR, with different genetic backgrounds. Constitutive expression of UGT368B2 was significantly higher in both resistant strains than in the sensitive strain. As resistant strains were able to deactivate benzimidazole anthelmintics via glycosylation more effectively then the sensitive strain, UGT368B2 enhanced constitutive expression might contribute to drug resistance in H. contortus.

Item Type:Articles
Additional Information:The work was supported by the Czech Science Foundation [17-11954Y] and by Charles University in Prague [PRIMUS/17/SCI/4, UNCE/18/SCI/012 and SVV 260 416]. Lucie Raisová Stuchlíková was supported by the project EFSA-CDN [CZ.02.1.01/0.0/0.0/16_019/0000841] co-funded by ERDF. Roz Laing is funded by a BBSRC strategic LoLa [BB/M003949/1].
Keywords:Detoxification, Haemonchus contortus, resistance, UDP-glycosyltransferase.
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Laing, Dr Roz
Authors: Matoušková, P., Lecová, L., Laing, R., Dimunová, D., Vogel, H., Raisová Stuchlíková, L., Nguyen, L. T., Kellerová, P., Vokřál, I., Lamka, J., Szotáková, B., Várady, M., and Skálová, L.
College/School:College of Medical Veterinary and Life Sciences > Institute of Biodiversity Animal Health and Comparative Medicine
Journal Name:International Journal for Parasitology: Drugs and Drug Resistance
Publisher:Elsevier
ISSN:2211-3207
ISSN (Online):2211-3207
Published Online:26 September 2018
Copyright Holders:Copyright © 2018 The Authors
First Published:First published in International Journal for Parasitology: Drugs and Drug Resistance 8(3): 420-429
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
636401The BUG consortium Building Upon the Genome: using H. contortus genomicresources to develop novel interventions to control endemic GI parasitesEileen DevaneyBiotechnology and Biological Sciences Research Council (BBSRC)BB/M003949/1RI BIODIVERSITY ANIMAL HEALTH & COMPMED