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dc.contributor.authorDubourg, Audrey
dc.contributor.authorXia, Dong
dc.contributor.authorWinpenny, John P
dc.contributor.authorAl Naimi, Suha
dc.contributor.authorBouzid, Maha
dc.contributor.authorSexton, Darren W
dc.contributor.authorWastling, Jonathan M
dc.contributor.authorHunter, Paul R
dc.contributor.authorTyler, Kevin M
dc.date.accessioned2020-07-29T16:30:01Z
dc.date.available2020-07-29T16:30:01Z
dc.date.issued2018-03
dc.identifier.citationDubourg , A , Xia , D , Winpenny , J P , Al Naimi , S , Bouzid , M , Sexton , D W , Wastling , J M , Hunter , P R & Tyler , K M 2018 , ' Giardia secretome highlights secreted tenascins as a key component of pathogenesis ' , GigaScience , vol. 7 , no. 3 , giy003 . https://doi.org/10.1093/gigascience/giy003en
dc.identifier.issn2047-217X
dc.identifier.otherPURE: 268917211
dc.identifier.otherPURE UUID: 52053b4c-34fc-4efd-933b-ac111f56b1be
dc.identifier.otherPubMed: 29385462
dc.identifier.otherPubMedCentral: PMC5887430
dc.identifier.otherScopus: 85050726583
dc.identifier.urihttp://hdl.handle.net/10023/20368
dc.description.abstractBackground: Giardia is a protozoan parasite of public health relevance that causes gastroenteritis in a wide range of hosts. Two genetically distinct lineages (assemblages A and B) are responsible for the human disease. Although it is clear that differences in virulence occur, the pathogenesis and virulence of Giardia remain poorly understood. Results: The genome of Giardia is believed to contain open reading frames that could encode as many as 6000 proteins. By successfully applying quantitative proteomic analyses to the whole parasite and to the supernatants derived from parasite culture of assemblages A and B, we confirm expression of ∼1600 proteins from each assemblage, the vast majority of which are common to both lineages. To look for signature enrichment of secreted proteins, we considered the ratio of proteins in the supernatant compared with the pellet, which defined a small group of enriched proteins, putatively secreted at a steady state by cultured growing trophozoites of both assemblages. This secretome is enriched with proteins annotated to have N-terminal signal peptide. The most abundant secreted proteins include known virulence factors such as cathepsin B cysteine proteases and members of a Giardia superfamily of cysteine-rich proteins that comprise variant surface proteins, high-cysteine membrane proteins, and a new class of virulence factors, the Giardia tenascins. We demonstrate that physiological function of human enteric epithelial cells is disrupted by such soluble factors even in the absence of the trophozoites. Conclusions: We are able to propose a straightforward model of Giardia pathogenesis incorporating key roles for the major Giardia-derived soluble mediators.
dc.format.extent13
dc.language.isoeng
dc.relation.ispartofGigaScienceen
dc.rightsCopyright © The Author(s) 2018. Published by Oxford University Press. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly citeden
dc.subjectAnimalsen
dc.subjectCell Lineage/geneticsen
dc.subjectExtracellular Matrix Proteins/geneticsen
dc.subjectGastroenteritis/geneticsen
dc.subjectGenome/geneticsen
dc.subjectGenotypeen
dc.subjectGiardia/geneticsen
dc.subjectGiardiasis/geneticsen
dc.subjectHumansen
dc.subjectNerve Tissue Proteins/geneticsen
dc.subjectPhylogenyen
dc.subjectProteomicsen
dc.subjectTenascin/geneticsen
dc.subjectQH426 Geneticsen
dc.subjectQR Microbiologyen
dc.subjectRA Public aspects of medicineen
dc.subjectDASen
dc.subject.lccQH426en
dc.subject.lccQRen
dc.subject.lccRAen
dc.titleGiardia secretome highlights secreted tenascins as a key component of pathogenesisen
dc.typeJournal articleen
dc.description.versionPublisher PDFen
dc.contributor.institutionUniversity of St Andrews. School of Medicineen
dc.identifier.doihttps://doi.org/10.1093/gigascience/giy003
dc.description.statusPeer revieweden


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