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Giardia secretome highlights secreted tenascins as a key component of pathogenesis

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Date
03/2018
Author
Dubourg, Audrey
Xia, Dong
Winpenny, John P
Al Naimi, Suha
Bouzid, Maha
Sexton, Darren W
Wastling, Jonathan M
Hunter, Paul R
Tyler, Kevin M
Keywords
Animals
Cell Lineage/genetics
Extracellular Matrix Proteins/genetics
Gastroenteritis/genetics
Genome/genetics
Genotype
Giardia/genetics
Giardiasis/genetics
Humans
Nerve Tissue Proteins/genetics
Phylogeny
Proteomics
Tenascin/genetics
QH426 Genetics
QR Microbiology
RA Public aspects of medicine
DAS
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Abstract
Background: 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.
Citation
Dubourg , 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/giy003
Publication
GigaScience
Status
Peer reviewed
DOI
https://doi.org/10.1093/gigascience/giy003
ISSN
2047-217X
Type
Journal article
Rights
Copyright © 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 cited
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  • University of St Andrews Research
URI
http://hdl.handle.net/10023/20368

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