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Transcriptional profiling of Giardia intestinalis in response to oxidative stress
Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Microbiology.
Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Microbiology.
Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Microbiology.
2015 (English)In: International Journal of Parasitology, ISSN 0020-7519, E-ISSN 1879-0135, Vol. 45, no 14, 925-938 p.Article in journal (Refereed) Published
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Abstract [en]

Giardia intestinalis is a microaerophilic parasite that infects the human upper small intestine, an environment that is fairly aerobic with reactive oxygen species being produced to fight off the parasite. It is quite perplexing how Giardia, lacking conventional eukaryotic antioxidant machinery (e.g. catalase, superoxide dismutase and glutathione peroxidase), can cope with the oxidative stress in this environment. We used transcriptomics (RNA sequencing and quantitative PCR) to study giardial gene expression changes in response to oxygen (O-2; 1 h) and hydrogen peroxide (H2O2; 150 mu M, 500 mu M and 1 mM for 1 h). The results showed phenotypic and transcriptional differences between Giardia isolates of different genotypes (WB, assemblage A and GS, assemblage B), with GS being more tolerant to H2O2 and exhibiting higher basic transcript levels of antioxidant genes (e.g. NADH oxidase lateral transfer candidate, peroxiredoxin 1 (Prxl) and thioredoxin (Trx)-like proteins). Cysteine is a major antioxidant in Giardia and its role in oxidative defense could be highlighted here by the up-regulation of gene transcripts encoding the cysteine-rich variable surface proteins (VSPs) and high cysteine membrane proteins (HCMPs). Genes in the thioredoxin system (Prxl, Trx and Trx reductase) occupied a central role in the gene expression response to oxidative stress, together with genes encoding metabolic (NADPH-producing enzymes, glutathione and glycerol biosynthetic enzymes) and O-2-consuming nitric oxide detoxification enzymes (e.g. nitroreductase, flavohemoprotein and a flavodiiron protein). This study reveals the intricate network of genes associated with the oxidative stress response in Giardia, and provides a stepping-stone towards future studies at the protein level.

Place, publisher, year, edition, pages
2015. Vol. 45, no 14, 925-938 p.
Keyword [en]
Giardia, Oxidative stress, RNA sequencing, Host-parasite interaction
National Category
Infectious Medicine
Identifiers
URN: urn:nbn:se:uu:diva-275479DOI: 10.1016/j.ijpara.2015.07.005ISI: 000367484000006OAI: oai:DiVA.org:uu-275479DiVA: diva2:900388
Funder
Swedish Research Council
Available from: 2016-02-04 Created: 2016-02-04 Last updated: 2017-11-30Bibliographically approved

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Ma'ayeh, Showgy Y.Svärd, Staffan G.

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