WP 3 Dissecting the commensal-to-pathogen shift and protection by probiotics in vivo

In WP3, we will use the same approaches described in WP2 (partner in Jena) (transcriptional profiling, “competitive phenomics”, metabolomics) as well as metagenomics and imaging technologies with fluorescent-labeled clinical strains to pinpoint the basic mechanisms of gastrointestinal tract colonization and the commensal-to-pathogenicity transition in an established murine model in vivo (Task 1) and to study how probiotic and commensal bacteria and yeasts can prevent pathogenicity of C. albicans in the in vivo model (Task 2). We expect to identify transcriptional and metabolomics patterns and factors associated with commensal growth and pathogenicity. Selected factors associated with the commensal-to-pathogen shift in the in vivo model will be analyzed in detail by our partner in Düsseldorf. Complementary, imaging technologies with fluorescent-labelled strains will be used to assess fitness and colonization attributes of selected C. albicans clinical strains in competition experiments and to test their potential to induce the “compath” shift.

References

Bonhomme J, Chauvel M, Goyard S et al. (2011) Contribution of the glycolytic flux and hypoxia adaptation to efficient biofilm formation by Candida albicans. Mol Microbiol 80, 995-1013.
PubMed Open Access PDF

Chauvel M, Nesseir A, Cabral V et al. (2012) A versatile overexpression strategy in the pathogenic yeast Candida albicans: Identification of regulators of morphogenesis and fitness. PLoS One 7, e45912.
PubMed Open Access PDF

Gutierrez-Escribano P, Zeidler U et al. (2012) The NDR/LATS kinase Cbk1 controls the activity of the transcriptional regulator Bcr1 during biofilm formation in Candida albicans. PLoS Pathog 8, e1002683.
PubMed Open Access PDF

Neville BA, d’Enfert C, Bougnoux ME (2015) Candida albicans commensalism in the gastrointestinal tract. FEMS Yeast Res 15, pii: fov081. PubMed

Vediyappan G, Rossignol T, d'Enfert C (2010) Interaction of Candida albicans biofilms with antifungals: transcriptional response and binding of antifungals to betaglucans. Antimic Ag Chemother 54, 2096-2111.
PubMed Open Access PDF

Znaidi S, Nesseir A, Chauvel M et al. (2013) Comprehensive functional portrait of two Heat Shock Factor-type transcriptional regulators involved in Candida albicans morphogenesis and virulence. PLoS Pathog 9, e1003519.
PubMed Open Access PDF

Related partners

Institut Pasteur Paris

Institut Pasteur Paris

Address

Institut Pasteur
25, rue du Docteur Roux
75015 Paris, France

Principal Investigator

Christophe d’ Enfert

Christophe d’ Enfert

+33 1 40 61 32 57

www.pasteur.fr

Scientists

Marie-Elisabeth Bougnoux

Marie-Elisabeth Bougnoux
Associate Professor

Natacha Sertour

Natacha Sertour
Technician

Murielle Chauvel

Murielle Chauvel
Technician

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Hans Knöll Institute Jena

Hans Knöll Institute Jena

Address

Leibniz Institute for Natural Product Research and Infection Biology
Hans Knöll Institute
Adolf-Reichwein-Str. 23
07745 Jena, Germany

Coordinator and Principal Investigator

Bernhard Hube

Bernhard Hube

+49 3641 532 1401

www.leibniz-hki.de

Scientists

Katja Graf

Katja Graf

+49 3641 532 1218

Antonia Dräger

Antonia Dräger

+49 3641 532 1595

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Heinrich Heine University Düsseldorf

Heinrich Heine University Düsseldorf

Address

Heinrich Heine University Düsseldorf
Universitätsstr. 1/26.12
40225 Düsseldorf, Germany

Principal Investigator

Scientists

Christoph Bürth

Christoph Bürth

+49 211 81-15488

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Universidad Complutense de Madrid

Universidad Complutense de Madrid (USM)

Address

Universidad Complutense de Madrid (USM)
Avda. Ramón y Cajal s/n
28040 Madrid, Spain

Principal Investigator

Jesús Pla

Jesús Pla

+34 91 3941617

www.ucm.es

Scientists

Elvira Román

Elvira Román

Daniel Prieto

Daniel Prieto

+34 610 686818

Rebeca Alonso Monge

Rebeca Alonso Monge

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Chalmers University of Technology Göteborg

Chalmers University of Technology Gothenborg

Address

Chalmers University of Technology
Kemivägen 10
41296 Gothenborg, Sweden

Principal Investigator

Jens Nielsen

Jens Nielsen

+46 31 772 3804

www.sysbio.se

Scientists

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