Project C1

Molecular characterisation of Candida albicans mucosal colonisation, infection and translocation

Project Description

Epithelial invasion and dissemination of C. albicans
Epithelial invasion and dissemination of C. albicans

The gut is believed to be the main reservoir of Candida albicans. In the majority of the human population the fungus exists in the gut as a harmless commensal. However, C. albicans can invade epithelial tissues of the gut to enter the bloodstream (translocation) due to immune dysfunctions or transient physiological alterations and damage (for example intestinal ischemia/hypoxia) or can reach the bloodstream due to epithelial damage caused by surgery, polytrauma or medical drug treatment. From the bloodstream, the fungus can infect almost all organs and can finally cause sepsis. It is not clear which physiological and immunological factors of the host and which attributes of C. albicans cause or favour such translocation through tissue. The aim of this project is to elucidate the molecular and cellular pathogenicity mechanisms, which are crucial for translocation of C. albicans through epithelial gut tissue into the blood stream. In the first part of the project, genome-wide transcription profiles of C. albicans during translocation will be obtained using established microarrays or RNAseq technologies and in vitro (translocation and damage of host cells), ex vivo (perfused gut) and in vivo (mouse) infection models for translocation established in project C5. Genes, whose expression is associated with colonisation or translocation will be analysed in detail with a focus on genes with previously unknown function. In parallel, large knock-out and overexpression mutant libraries will be screened in the established infection models. Genes necessary for translocation will be analysed in detail. It is expected that fungal factors will be identified, which are crucial for adhesion, primary invasion of epithelial cells, epithelial dissemination, proliferation within tissue, cell damage or immune evasion during interaction with phagocytes and which have distinct roles for fungal translocation. Factors, which are essential for translocation, represent potential drug targets, but may also be characteristic biomarkers indicating a translocation.

Principal Investigators

Prof. Dr. Bernhard Hube
Prof. Dr. Bernhard Hube

Department of Microbial Pathogenicity
Friedrich Schiller University Jena

Department Microbial Pathogenicity Mechanisms
Leibniz Institute for Natural Product Research and Infection Biology - Hans-Knöll-Institute

Dr. J. Christian Pérez
Dr. J. Christian Pérez

Institute for Molecular Infection Biology  

Julius Maximilians University Würzburg


Author Year Title Journal Links

Jacobsen ID, Lüttich A, Kurzai O, Hube B, Brock M


In vivo imaging of disseminated murine Candida albicans infection reveals unexpected host sites of fungal persistence during antifungal therapy.

J Antimicrob Chemother 69: 2785-96

Polke M, Hube B, Jacobsen ID 2015 Candida survival strategies.

Adv Appl Microbiol 91: 139-235

Hebecker B, Naglik JR, Hube B, Jacobsen ID 2014 Pathogenicity mechanisms and host response during oral Candida albicans infections. Expert Rev Anti Infect Ther 12: 867-79 PubMed
Wartenberg A, Linde J, Martin R, Schreiner M, Horn F, Jacobsen ID, Jenull S, Wolf T, Kuchler K, Guthke R, Kurzai O, Forche A, d'Enfert C, Brunke S, Hube B 2014

Microevolution of Candida albicans in macrophages restores filamentation in a nonfilamentous mutant.

PLoS Genet 10: e1004824

Mech F, Wilson D, Lehnert T, Hube B, Figge MT 2014

Epithelial invasion outcompetes hypha development during Candida albicans infection as revealed by an image-based systems biology approach.

Cytometry A 85: 126-39 PubMed
Ramachandra S, Linde J, Brock M, Guthke R, Hube B, Brunke S 2014

Regulatory networks controlling nitrogen sensing and uptake in Candida albicans.

PLoS One 9: e92734 PubMed
Ene IV, Brunke S, Brown AJ, Hube B 2014

Metabolism in fungal pathogenesis.

Cold Spring Harb Perspect Med 4: a019695

Moyes DL, Wilson D, Richardson JP, Mogavero S, Tang SX, Wernecke J, Höfs S, Gratacap RL, Robbins J, Runglall M, Murciano C, Blagojevic M, Thavaraj S, Förster TM, Hebecker B, Kasper L, Vizcay G, Iancu SI, Kichik N, Häder A, Kurzai O, Luo T, Krüger T, Kniemeyer O, Cota E, Bader O, Wheeler RT, Gutsmann T, Hube B, Naglik JR 2016

Candidalysin is a fungal peptide toxin critical for mucosal infection.

Nature 532: 64-8 PubMed
Hebecker B, Vlaic S, Conrad T, Bauer M, Brunke S, Kapitan M, Linde J, Hube B, Jacobsen ID 2016 Dual-species transcriptional profiling during systemic candidiasis reveals organ-specific host-pathogen interactions. Sci Rep 6: 36055 PubMed
Polke M, Sprenger M, Scherlach K, Albán-Proaño MC, Martin R, Hertweck C, Hube B, Jacobsen ID 2017 A functional link between hyphal maintenance and quorum sensing in Candida albicans.

Mol Microbiol 103: 595-617

Luo T, Krüger T, Knüpfer U, Kasper L, Wielsch N, Hube B, Kortgen A, Bauer M, Giamarellos-Bourboulis EJ, Dimopoulos G, Brakhage AA, Kniemeyer O 2016 Immunoproteomic analysis of antibody responses to extracellular proteins of Candida albicans revealing the importance of glycosylation for antigen recognition. J Proteome Res 15: 2394-406 PubMed
Gerwien F, Safyan A, Wisgott S, Hille F, Kaemmer P, Linde J, Brunke S, Kasper L, Hube B 2016 A novel hybrid iron regulation network combines features from pathogenic and nonpathogenic yeasts.

mBio 7(5) pii: e01782-16

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: 1709-15

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 PubMed
Ramírez-Zavala B, Mottola A, Haubenreißer J, Schneider S, Allert S, Brunke S, Ohlsen K, Hube B, Morschhäuser J 2017 The Snf1-activating kinase Sak1 is a key regulator of metabolic adaptation and in vivo fitness of Candida albicans. Mol Microbiol 104: 989-1007 PubMed
Wolf T, Kämmer P, Brunke S, Linde J 2017 Two's company: Studying interspecies relationships with dual RNA-seq.

Curr Opin Microbiol 42: 7-12


Gerwien F, Skrahina V, Kasper L, Hube B, Brunke S


Metals in fungal virulence.

FEMS Microbiol Rev 42


Jacobsen ID, Hube B 2017 Candida albicans morphology: still in focus. Expert Rev Anti Infect Ther 15: 327-30 (Editorial) PubMed
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 pii: eaam8834 PubMed

Skrahina V, Brock M, Hube B, Brunke S


Candida albicans Hap43 domains are required under iron starvation but not excess.

Front Microbiol 8: 2388


Malavia D, Lehtovirta-Morley LE, Alamir O, Weiß E, Gow NAR, Hube B, Wilson D


Zinc limitation induces a hyper-adherent goliath phenotype in Candida albicans.

Front Microbiol 8: 2238