Integrated bioinformatic and targeted deletion analyses of the SRS gene superfamily identify SRS29C as a negative regulator of Toxoplasma virulence.
Identifieur interne : 001200 ( Main/Exploration ); précédent : 001199; suivant : 001201Integrated bioinformatic and targeted deletion analyses of the SRS gene superfamily identify SRS29C as a negative regulator of Toxoplasma virulence.
Auteurs : James D. Wasmuth [Canada] ; Viviana Pszenny ; Simon Haile ; Emily M. Jansen ; Alexandra T. Gast ; Alan Sher ; Jon P. Boyle ; Martin J. Boulanger ; John Parkinson ; Michael E. GriggSource :
- mBio [ 2150-7511 ] ; 2012.
English descriptors
- KwdEn :
- Animals, Computational Biology (methods), Disease Models, Animal, Female, Gene Deletion, Gene Expression Profiling, Host-Pathogen Interactions, Mice, Protozoan Proteins (genetics), Sequence Deletion, Toxoplasma (genetics), Toxoplasma (pathogenicity), Toxoplasmosis, Animal (parasitology), Transcription Factors (genetics), Virulence, Virulence Factors (biosynthesis).
- MESH :
- chemical , biosynthesis : Virulence Factors.
- chemical , genetics : Protozoan Proteins, Transcription Factors.
- genetics : Toxoplasma.
- methods : Computational Biology.
- parasitology : Toxoplasmosis, Animal.
- pathogenicity : Toxoplasma.
- Animals, Disease Models, Animal, Female, Gene Deletion, Gene Expression Profiling, Host-Pathogen Interactions, Mice, Sequence Deletion, Virulence.
Abstract
The Toxoplasma gondii SRS gene superfamily is structurally related to SRS29B (formerly SAG1), a surface adhesin that binds host cells and stimulates host immunity. Comparative genomic analyses of three Toxoplasma strains identified 182 SRS genes distributed across 14 chromosomes at 57 genomic loci. Eight distinct SRS subfamilies were resolved. A core 69 functional gene orthologs were identified, and strain-specific expansions and pseudogenization were common. Gene expression profiling demonstrated differential expression of SRS genes in a developmental-stage- and strain-specific fashion and identified nine SRS genes as priority targets for gene deletion among the tissue-encysting coccidia. A Δsag1 sag2A mutant was significantly attenuated in murine acute virulence and showed upregulated SRS29C (formerly SRS2) expression. Transgenic overexpression of SRS29C in the virulent RH parent was similarly attenuated. Together, these findings reveal SRS29C to be an important regulator of acute virulence in mice and demonstrate the power of integrated genomic analysis to guide experimental investigations.
DOI: 10.1128/mBio.00321-12
PubMed: 23149485
Affiliations:
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Comparative genomic analyses of three Toxoplasma strains identified 182 SRS genes distributed across 14 chromosomes at 57 genomic loci. Eight distinct SRS subfamilies were resolved. A core 69 functional gene orthologs were identified, and strain-specific expansions and pseudogenization were common. Gene expression profiling demonstrated differential expression of SRS genes in a developmental-stage- and strain-specific fashion and identified nine SRS genes as priority targets for gene deletion among the tissue-encysting coccidia. A Δsag1 sag2A mutant was significantly attenuated in murine acute virulence and showed upregulated SRS29C (formerly SRS2) expression. Transgenic overexpression of SRS29C in the virulent RH parent was similarly attenuated. Together, these findings reveal SRS29C to be an important regulator of acute virulence in mice and demonstrate the power of integrated genomic analysis to guide experimental investigations.</div></front></TEI><affiliations><list><country><li>Canada</li></country><region><li>Ontario</li></region><settlement><li>Toronto</li></settlement><orgName><li>Université de Toronto</li></orgName></list><tree><noCountry><name sortKey="Boulanger, Martin J" sort="Boulanger, Martin J" uniqKey="Boulanger M" first="Martin J" last="Boulanger">Martin J. Boulanger</name><name sortKey="Boyle, Jon P" sort="Boyle, Jon P" uniqKey="Boyle J" first="Jon P" last="Boyle">Jon P. Boyle</name><name sortKey="Gast, Alexandra T" sort="Gast, Alexandra T" uniqKey="Gast A" first="Alexandra T" last="Gast">Alexandra T. Gast</name><name sortKey="Grigg, Michael E" sort="Grigg, Michael E" uniqKey="Grigg M" first="Michael E" last="Grigg">Michael E. Grigg</name><name sortKey="Haile, Simon" sort="Haile, Simon" uniqKey="Haile S" first="Simon" last="Haile">Simon Haile</name><name sortKey="Jansen, Emily M" sort="Jansen, Emily M" uniqKey="Jansen E" first="Emily M" last="Jansen">Emily M. Jansen</name><name sortKey="Parkinson, John" sort="Parkinson, John" uniqKey="Parkinson J" first="John" last="Parkinson">John Parkinson</name><name sortKey="Pszenny, Viviana" sort="Pszenny, Viviana" uniqKey="Pszenny V" first="Viviana" last="Pszenny">Viviana Pszenny</name><name sortKey="Sher, Alan" sort="Sher, Alan" uniqKey="Sher A" first="Alan" last="Sher">Alan Sher</name></noCountry><country name="Canada"><region name="Ontario"><name sortKey="Wasmuth, James D" sort="Wasmuth, James D" uniqKey="Wasmuth J" first="James D" last="Wasmuth">James D. Wasmuth</name></region></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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