Project C1

Molecular characterisation of Candida albicans mucosal colonisation, infection and translocation

Candida albicans can colonize multiple niches of the human body without symptoms, but it can also infect epithelial tissues or enter the bloodstream causing systemic infections. In the first funding period, C1 established a translocation model, identified and characterized factors required for epithelial damage and translocation, including a novel pore-producing toxin, and characterized the translocation process. C1 will continue and extend this project by investigating niche-specific factors and regulatory networks required for colonization or infection and will elucidate the mechanisms crucial for invasion, damage and translocation.

Candida albicans hyphae invading human epithelium. From: Cover photograph (Copyright © 2014, American Society for Microbiology. All Rights Reserved.): Eukaryot Cell. 2014 Aug; 13(8): Cover
Candida albicans hyphae invading human epithelium. From: Cover photograph (Copyright © 2014, American Society for Microbiology. All Rights Reserved.): Eukaryot Cell. 2014 Aug; 13(8): Cover
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  

bernhard.hube@leibniz-hki.de

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

Institute for Molecular Infection Biology  

Julius Maximilians University Würzburg

christian.perez@uni-wuerzburg.de

Publications
Author Year Title Journal Links
Gerwien F, Skrahina V, Kasper L, Hube B, Brunke S 2018 Metals in fungal virulence. FEMS Microbiol Rev 42 PubMed
Richardson JP, Mogavero S, Moyes DL, Blagojevic M, Krüger T, Verma AH, Coleman BM, De La Cruz Diaz J, Schulz D, Ponde NO, Carrano G, Kniemeyer O, Wilson D, Bader O, Enoiu SI, Ho J, Kichik N, Gaffen SL, Hube B, Naglik J 2018 Processing of Candida albicans Ece1p is critical for Candidalysin maturation and fungal virulence. mBio 9: pii: e02178-17 PubMed
Meir J, Hartmann E, Eckstein MT, Guiducci E, Kirchner F, Rosenwald A, LeibundGut‐Landmann S, Pérez JC 2018 Identification of Candida albicans regulatory genes governing mucosal infection. Cell Microbiol 20: e12841 PubMed
Allert S*, Förster TM*, Svensson CM, Richardson JP, Pawlik T, Hebecker B, Rudolphi S, Juraschitz M, Schaller M, Blagojevic M, Morschhäuser J, Figge MT, Jacobsen ID, Naglik JR, Kasper L, Mogavero S, Hube B; *authors contributed equally 2018 Candida albicans-induced epithelial damage mediates translocation through intestinal barriers. mBio 9: e00915-18 PubMed
Kasper L, König A, Koenig PA, Gresnigt MS, Westman J, Drummond, RA, Lionakis MS, Groß O, Ruland J, Naglik, JR, Hube B 2018 The fungal peptide toxin Candidalysin activates the NLRP3 inflammasome and causes cytolysis in mononuclear phagocytes. Nat Commun [In press] Nat Commun
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 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 PubMed
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 2017 Candida albicans Hap43 domains are required under iron starvation but not excess. Front Microbiol 8: 2388 PubMed
Malavia D, Lehtovirta-Morley LE, Alamir O, Weiß E, Gow NAR, Hube B, Wilson D 2017 Zinc limitation induces a hyper-adherent goliath phenotype in Candida albicans. Front Microbiol 8: 2238 PubMed
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
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 PubMed
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 PubMed
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
Polke M, Hube B, Jacobsen ID 2015 Candida survival strategies. Adv Appl Microbiol 91: 139-235 PubMed
Jacobsen ID, Lüttich A, Kurzai O, Hube B, Brock M 2014 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 PubMed
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 PubMed
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 PubMed