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Giardia intestinalis Elongation Factor 1-alpha is released during host cell interaction
Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Microbiology. (Prof. Staffan Svärd)
Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Microbiology. (Prof. Staffan Svärd)
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , Ludwig Institute for Cancer Research. (group leader)
Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Microbiology. (group leader)
(English)Manuscript (preprint) (Refereed)
Abstract [en]

Giardia intestinalis is an intestinal diarrhea-causing parasite but the disease mechanism is not fully understood. Here we used SDS-PAGE gels and MALDI-TOF analysis to identify proteins released by Giardia trophozoites during axenic growth with and without host cells. We detected serum proteins that bind strongly to the parasite surface but also two Giardia proteins: elongation factor-1 alpha (EF-1α) and a 58kDa protein identified as arginine deiminase (ADI). Two genes encoding EF-1α were detected in the Giardia WB genome 35kbp apart. The coding sequences are identical but the promoter and 3’ regions differ. Promoter luciferase-fusions showed that both genes are transcribed in trophozoites. The EF-1α protein localizes to the ER region but it relocalizes to the plasma membrane and is secreted during host cell interaction. Recombinant EF-1α is recognized by serum from giardiasis patients. Our results suggest that EF-1α is important during Giardia infections and that ADI can be the earlier identified 58kDa enterotoxin.

National Category
Infectious Medicine Biochemistry and Molecular Biology
Research subject
Microbiology
Identifiers
URN: urn:nbn:se:uu:diva-109888OAI: oai:DiVA.org:uu-109888DiVA: diva2:274448
Available from: 2009-10-29 Created: 2009-10-29 Last updated: 2010-01-14
In thesis
1. Host-Pathogen Responses during Giardia infections
Open this publication in new window or tab >>Host-Pathogen Responses during Giardia infections
2009 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Giardia lamblia is a eukaryotic parasite of the upper small intestine of humans and animals. The infecting trophozoite cells do not invade the epithelium lining of the intestine, but attach to the brush border surface in the intestinal lumen. The giardiasis disease in humans is highly variable. Prior to this study, the molecular mechanisms involved in establishment of infection or cause of disease were largely uncharacterized.

In this thesis, the molecular relationship between Giardia and the human host is described. The interaction of the parasite with human epithelial cells was investigated in vitro. Changes in the transcriptome and proteome of the parasite and the host cells, and changes in the micro-environment of the infection have been identified using microarray technology, and 1- and 2-Dimensional SDS-PAGE protein mapping together with mass spectrometry identification.

The first large-scale description of cellular activities within host epithelial cells during Giardia infection is included in this thesis (Paper I). We identified a unique activation of the host immune response and induction of apoptosis upon infection by Giardia. Four important virulence factors of the parasite, directly linked to the success of Giardia infection, were characterized and are presented in Papers II and III. The parasite was shown to have immune-modulating capacities, and to release proteins during host-interaction that facilitate the establishment of infection. Additional putative virulence factors were found among Giardia genes transcriptionally up-regulated during early infection (Paper IV).

In summary, this thesis provides important insights into the molecular mechanisms of the host-parasite interaction.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2009. 71 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Science and Technology, ISSN 1651-6214 ; 689
Keyword
Giardia, parasite infection, host-parasite releationship, immune activation, virulence factor, immune evasion
National Category
Biochemistry and Molecular Biology Microbiology
Research subject
Microbiology
Identifiers
urn:nbn:se:uu:diva-108980 (URN)978-91-554-7652-6 (ISBN)
Public defence
2009-12-12, B41, Biomedicinskt Centrum, Husargatan 3, Uppsala, 10:00 (English)
Opponent
Supervisors
Available from: 2009-11-19 Created: 2009-10-06 Last updated: 2009-11-19Bibliographically approved

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