dc.contributor.author
Yilmaz, Esra
dc.contributor.author
Ramünke, Sabrina
dc.contributor.author
Demeler, Janina
dc.contributor.author
Krücken, Jürgen
dc.date.accessioned
2018-06-08T10:26:00Z
dc.date.available
2017-11-09T10:47:50.221Z
dc.identifier.uri
https://refubium.fu-berlin.de/handle/fub188/20430
dc.identifier.uri
http://dx.doi.org/10.17169/refubium-23733
dc.description.abstract
Benzimidazoles (BZs) remain amongst the most widely used anthelmintic drug
classes against gastro-intestinal nematode infections, although their efficacy
is increasingly compromised by resistance. The primary underlying mechanisms
for BZ resistance are single-nucleotide polymorphisms (SNPs) in the isotype 1
β-tubulin gene causing the substitutions F167Y, E198A or F200Y. However,
resistance is believed to be multi-genic and previous studies have shown that
isolates carrying 90–100% F200Y can vary considerably in their resistance
level in the egg hatch assay (EHA). Cytochrome P450 monooxygenases (CYPs) are
associated with drug resistance in mammals and arthropods and have been
considered as mediators of anthelmintic resistance. In Caenorhabditis elegans,
several members of the CYP34/35 and CYP31 families are BZ and/or xenobiotic
inducible and thiabendazole (TBZ) is metabolised by CYP35D1. Here, expression
of all 5 CYPs closely related to the C. elegans CYP34/35 and CYP31 families
was investigated in fourth-stage larvae of two susceptible and three BZ-
resistant Haemonchus contortus isolates following in vitro exposure to TBZ for
3 and 6 h using real-time RT-PCR. The resistance status of all isolates was
determined using EHAs and quantification of resistance-associated β-tubulin
SNPs using pyrosequencing. While none of the CYPs was TBZ inducible,
constitutive expression of CYP34/35 family member HCOI100383400 was
significantly 2.4–3.7-fold higher in the multi-drug resistant WR isolate with
the strongest BZ resistance phenotype compared to susceptible and
intermediate-level BZ-resistant isolates. Although this increase is only
moderate, HCOI100383400 might still be involved in high-level BZ resistance by
further decreasing susceptibility in isolates already carrying 100% of a
β-tubulin SNP causing BZ resistance. Lower transcript levels were observed for
all CYPs in the intermediately resistant IRE isolate in comparison to the
susceptible HcH isolate, which, except for CYP HCOI01579500, were
statistically non-significant. This suggests that none of the investigated
CYPs may contribute to protection against TBZ in this particular isolate.
en
dc.format.extent
8 Seiten
dc.rights.uri
http://creativecommons.org/licenses/by/4.0/
dc.subject.ddc
600 Technik, Medizin, angewandte Wissenschaften::630 Landwirtschaft
dc.title
Comparison of constitutive and thiabendazole-induced expression of five
cytochrome P450 genes in fourth-stage larvae of Haemonchus contortus isolates
with different drug susceptibility identifies one gene with high constitutive
expression in a multi-resistant isolate
dc.type
Wissenschaftlicher Artikel
dcterms.bibliographicCitation
International Journal for Parasitology: Drugs and Drug Resistance. - 7 (2017),
3, S. 362-369
dcterms.bibliographicCitation.doi
10.1016/j.ijpddr.2017.10.001
dcterms.bibliographicCitation.url
http://doi.org/10.1016/j.ijpddr.2017.10.001
refubium.affiliation
Veterinärmedizin
de
refubium.affiliation.other
Institut für Parasitologie und Tropenveterinärmedizin
refubium.funding
Deutsche Forschungsgemeinschaft (DFG)
refubium.mycore.fudocsId
FUDOCS_document_000000028390
refubium.note.author
Gefördert durch die DFG und den Open-Access-Publikationsfonds der Freien
Universität Berlin.
refubium.resourceType.isindependentpub
no
refubium.mycore.derivateId
FUDOCS_derivate_000000009049
dcterms.accessRights.openaire
open access
dcterms.isPartOf.issn
2211-3207