Giardia secretome highlights secreted tenascins as a key component of pathogenesis

Audrey Dubourg, Dong Xia, John P. Winpenny, Suha Al Naimi, Maha Bouzid, Darren W. Sexton, Jonathan M. Wastling, Paul R. Hunter, Kevin M. Tyler*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

49 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1-13
Number of pages13
JournalGigaScience
Volume7
Issue number3
DOIs
Publication statusPublished - 1 Mar 2018
Externally publishedYes

Bibliographical note

Publisher Copyright:
© The Author(s) 2018.

Keywords

  • Cysteine protease
  • Enteric pathogen
  • Giardia
  • Proteomics
  • Quantitative proteomics
  • Secretion
  • Tenascin

Fingerprint

Dive into the research topics of 'Giardia secretome highlights secreted tenascins as a key component of pathogenesis'. Together they form a unique fingerprint.

Cite this