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Giardia Secretome Highlights Secreted Tenascins as a Key Component of Pathogenesis

Wastling

Giardia Secretome Highlights Secreted Tenascins as a Key Component of Pathogenesis Thumbnail


Authors

Wastling



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.

Acceptance Date Jan 29, 2018
Publication Date Jan 29, 2018
Publicly Available Date Mar 29, 2024
Journal GigaScience
Publisher Oxford University Press
DOI https://doi.org/10.1093/gigascience/giy003
Keywords Giardia, Secretion, Proteomics, Quantitative Proteomics, Tenascin, Cysteine protease, Enteric Pathogen.
Publisher URL https://academic.oup.com/gigascience/advance-article/doi/10.1093/gigascience/giy003/4818238

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