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dc.contributor.authorMa, Guangxu
dc.contributor.authorWang, Tao
dc.contributor.authorKorhonen, Pasi K
dc.contributor.authorNie, Shuai
dc.contributor.authorReid, Gavin E
dc.contributor.authorStroehlein, Andreas J
dc.contributor.authorKoehler, Anson V
dc.contributor.authorChang, Bill CH
dc.contributor.authorHofmann, Andreas
dc.contributor.authorYoung, Neil D
dc.contributor.authorGasser, Robin B
dc.date.accessioned2019-07-04T12:33:18Z
dc.date.available2019-07-04T12:33:18Z
dc.date.issued2019
dc.identifier.issn1756-3305
dc.identifier.doi10.1186/s13071-018-3265-y
dc.identifier.urihttp://hdl.handle.net/10072/382749
dc.description.abstractBackground Toxocara canis is quite closely related to Ascaris suum but its biology is more complex, involving a phase of arrested development (diapause or hypobiosis) in tissues as well as transplacental and transmammary transmission routes. In the present study, we explored and compared dauer-like signalling pathways of T. canis and A. suum to infer which components in these pathways might associate with, or regulate, this added complexity in T. canis. Methods Guided by information for Caenorhabditis elegans, we bioinformatically inferred and compared components of dauer-like signalling pathways in T. canis and A. suum using genomic and transcriptomic data sets. In these two ascaridoids, we also explored endogenous dafachronic acids (DAs), which are known to be critical in regulating larval developmental processes in C. elegans and other nematodes, by liquid chromatography-mass spectrometry (LC-MS). Results Orthologues of C. elegans dauer signalling genes were identified in T. canis (n = 55) and A. suum (n = 51), inferring the presence of a dauer-like signalling pathway in both species. Comparisons showed clear differences between C. elegans and these ascaridoids as well as between T. canis and A. suum, particularly in the transforming growth factor-β (TGF-β) and insulin-like signalling pathways. Specifically, in both A. suum and T. canis, there was a paucity of genes encoding SMAD transcription factor-related protein (daf-3, daf-5, daf-8 and daf-14) and insulin/insulin-like peptide (daf-28, ins-4, ins-6 and ins-7) homologues, suggesting an evolution and adaptation of the signalling pathway in these parasites. In T. canis, there were more orthologues coding for homologues of antagonist insulin-like peptides (Tc-ins-1 and Tc-ins-18), an insulin receptor substrate (Tc-ist-1) and a serine/threonine kinase (Tc-akt-1) than in A. suum, suggesting potentiated functional roles for these molecules in regulating larval diapause and reactivation. A relatively conserved machinery was proposed for DA synthesis in the two ascaridoids, and endogenous Δ4- and Δ7-DAs were detected in them by LC-MS analysis. Differential transcription analysis between T. canis and A. suum suggests that ins-17 and ins-18 homologues are specifically involved in regulating development and migration in T. canis larvae in host tissues. Conclusion The findings of this study provide a basis for functional explorations of insulin-like peptides, signalling hormones (i.e. DAs) and related nuclear receptors, proposed to link to development and/or parasite-host interactions in T. canis. Elucidating the functional roles of these molecules might contribute to the discovery of novel anthelmintic targets in ascaridoids.
dc.description.peerreviewedYes
dc.languageEnglish
dc.language.isoeng
dc.publisherBMC
dc.relation.ispartofpagefrom1
dc.relation.ispartofpageto10
dc.relation.ispartofissue32
dc.relation.ispartofjournalPARASITES & VECTORS
dc.relation.ispartofvolume12
dc.subject.fieldofresearchMedical Microbiology
dc.subject.fieldofresearchPublic Health and Health Services
dc.subject.fieldofresearchcode1108
dc.subject.fieldofresearchcode1117
dc.subject.keywordsToxocara canis
dc.subject.keywordsAscaris suum
dc.subject.keywordsDauer signalling pathway
dc.subject.keywordsDafachronic acid
dc.subject.keywordsArrested development
dc.titleComparative bioinformatic analysis suggests that specific dauer-like signalling pathway components regulate Toxocara canis development and migration in the mammalian host
dc.typeJournal article
dc.type.descriptionC1 - Articles
dc.type.codeC - Journal Articles
dcterms.licensehttp://creativecommons.org/licenses/by/4.0/
gro.rights.copyright© The Author(s). 2019 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
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gro.griffith.authorHofmann, Andreas


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