WP 2 Dissecting the commensal-to-pathogen shift and protection by probiotics ex vivo

In WP2, we will use cutting-edge genome-wide approaches, functional genomics and metabolomics to investigate the transition of C. albicans from commensalism to pathogenicity ex vivo. We will establish a commensal model consisting of gut bacteria (Lactobacilli and E. coli) and C. albicans on enterocytes. Antibiotics will then be used to trigger the commensal-to-pathogen shift. RNAseq will be used to identify fungal, bacterial and host transcriptional patterns, including the dynamics of the expression of metabolic genes. Samples will be taken for targeted metabolome analysis to build and confirm the metabolic model. Variations in the components of the interaction will allow the dissection of crosstalk between bacteria, enterocytes and C. albicans and the impact of antibiotics. “Competitive phenomics” based on pools of barcoded, engineered and clinical C. albicans strains will be used to identify strains with increased or decreased fitness in the ex vivo model. Furthermore, we will explore how probiotic and commensal bacteria and yeasts can prevent C. albicans infections or reverse the shift from pathogenicity to commensalism.

References

Almeida RS, Brunke S et al. (2008) The hyphal-associated adhesin and invasin Als3 of Candida albicans mediates iron acquisition from host ferritin. PLoS Pathog 4, e1000217.
PubMed Open Access PDF

Allert S, Brunke S, Hube B (2016) In vivo transcriptional profiling of human pathogenic fungi during infection: Reflecting the real life? PLoS Pathog 12, e1005471. (Review)
PubMed Open Access

Brunke S, Mogavero S, Kasper L, Hube B (2016) Virulence factors in fungal pathogens of man. Curr Opin Microbiol 32, 89-95. (Review)
PubMed Open Access

Butler G, Rasmussen MD et al. (2009) Evolution of pathogenicity and sexual reproduction in eight Candida genomes. Nature 459, 657-662.
PubMed Open Access PDF

Citiulo F, Jacobsen ID et al. (2012) Candida albicans scavenges host zinc via Pra1 during endothelial invasion. PLoS Pathog 8, e1002777.
PubMed Open Access PDF

Förster TM, Mogavero S, Dräger A, Graf K, Polke M, Jacobsen ID, Hube B (2016) Enemies and brothers in arms: Candida albicans and gram-positive bacteria. Cell Microbiol 18, 1709-1715.
PubMed

Höfs S, Mogavero S, Hube B (2016) Interaction of Candida albicans with host cells: virulence factors, host defence, escape strategies and the microbiota. J Microbiol 54, 149-169. (Review) PubMed

Mayer FL, Wilson D et al. (2012) The novel Candida albicans transporter Dur31 is a multi-stage pathogenicity factor. PLoS Pathog 8, e1002592.
PubMed Open Access PDF

Seider K, Brunke S et al. (2011) The facultative intracellular pathogen Candida glabrata subverts macrophage cytokine production and phagolysosome maturation. J Immunol 187, 3072-3086.
PubMed Open Access PDF

Verma AH, Richardson JP, Zhou C, Coleman BM, Moyes DL, Ho J, Huppler AR, Ramani K, McGeachy MJ, Mufazalov IA, Waisman A, Kane LP, Biswas PS, Hube B, Naglik JR, Gaffen SL (2017) Oral epithelial cells orchestrate innate type 17 responses to Candida albicans through the virulence factor candidalysin. Sci Immunol 2(17), pii: eaam8834. PubMed

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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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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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Universidad Complutense de Madrid

Universidad Complutense de Madrid (USM)

Address

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

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Jesús Pla

Jesús Pla

+34 91 3941617

www.ucm.es

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Elvira Román

Elvira Román

Daniel Prieto

Daniel Prieto

+34 610 686818

Rebeca Alonso Monge

Rebeca Alonso Monge

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Chalmers University Göteborg

Chalmers University of Technology Gothenborg

Address

Chalmers University of Technology
Kemivägen 10
41296 Gothenborg, Sweden

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Jens Nielsen

Jens Nielsen

+46 31 772 3804

www.sysbio.se

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