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Differential expression of beta-tubulin isotypes in different life stages of Parascaris spp after exposure to thiabendazole

Tyden, Eva and Skarin, Moa and Andersson Franko, Mikael and Höglund, Johan (2016). Differential expression of beta-tubulin isotypes in different life stages of Parascaris spp after exposure to thiabendazole. Molecular and biochemical parasitology. 205:1-2, 22-28
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Abstract

Anthelmintic resistance (AR) to macrocyclic lactones (ML) has been described in Parascaris of horses world-wide. In contrast, benzimidazoles (BZ) are still effective, although reduced efficacy to this drug class was recently reported. The mode of action of BZ is binding to beta-tubulin, which prevents polymerisation of microtubules. In this study, beta-tubulin gene expression of isotypes 1 and 2 was investigated at seven time points (0, 6, 24, 72, 96 and 120h) during embryogenesis and in adult worms. In addition, an in ovo larval developmental test was developed to study beta-tubulin gene expression of both isotypes in parasacaris eggs after exposure to different concentrations of thiabendazole (TBZ) for five days at 25 degrees C. A strong pattern of differential expression of beta-tubulin and isotype 1 was observed in all stages, while isotype 2 expression was mainly found at an early phase of the embryogenesis. For isotype 1, a 5-fold increase was observed during the first 48 h, but gene expression gradually decreased after 72, 96 and 120 h. Isotype 2 was only expressed during the first 24 h, followed by a 130-fold decrease at (time points) 72, 96 and 120 h. The in ovo larval developmental test, in which we exposed initially unembryonated eggs to increased concentrations of TBZ, did affect isotype I gene expression but not isotype 2. This assumes that each isotype has specific functions in different life stages. This is in agreement with the 'multi-tubulin' hypothesis, which states that different tubulin isotypes are required for specialised microtubule functions. Isotype I is the most likely drug target for BZs, as isotype 2 was only expressed at very low levels later in development. Increasing concentrations of TBZ altered beta-tubulin isotype 1 gene expression after exposure of the eggs for five days, but this was not seen for isotype 2.

Authors/Creators:Tyden, Eva and Skarin, Moa and Andersson Franko, Mikael and Höglund, Johan
Title:Differential expression of beta-tubulin isotypes in different life stages of Parascaris spp after exposure to thiabendazole
Series/Journal:Molecular and biochemical parasitology (BIB9033542)
Year of publishing :2016
Volume:205
Number:1-2
Page range:22-28
Number of Pages:7
Publisher:Elsevier
Associated Programs and Other Stakeholders:SLU - Research Areas for the Future > Future Animal Health and Welfare
ISSN:0166-6851
Language:English
Publication Type:Journal article
Refereed:Yes
Article category:Scientific peer reviewed
Version:Published version
Full Text Status:Public
Subjects:(A) Swedish standard research categories 2011 > 3 Medical and Health Sciences > 301 Basic Medicine > Other Basic Medicine
(A) Swedish standard research categories 2011 > 4 Agricultural Sciences > 403 Veterinary Science > Other Veterinary Science
Agrovoc terms:Parascaris, parasitology
Keywords:Parascaris spp, beta-tubulin, Gene expression, Life stages, Embryogenesis, Thiabendazole
URN:NBN:urn:nbn:se:slu:epsilon-e-3979
Permanent URL:
http://urn.kb.se/resolve?urn=urn:nbn:se:slu:epsilon-e-3979
Additional ID:
Type of IDID
Web of Science (WoS)000375498600004
DOI10.1016/j.molbiopara.2016.02.004
ID Code:14081
Faculty:NJ - Fakulteten för naturresurser och jordbruksvetenskap
VH - Faculty of Veterinary Medicine and Animal Science
Department:(NL, NJ) > Dept. of Economics
(VH) > Dept. of Biomedical Sciences and Veterinary Public Health
Deposited By: SLUpub Connector
Deposited On:23 Feb 2017 10:44
Metadata Last Modified:23 Feb 2017 10:44

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