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
Publications
Author Year Title Journal Links
Schimanski J, Gresnigt MS, Brunner E, Werz O, Hube B, Garscha U 2024 Hyphal-associated protein expression is crucial for Candida albicans-induced eicosanoid biosynthesis in immune cells. Eur J Immunol:e2350743 PubMed
Lange T, Kasper L, Gresnigt MS, Brunke S, Hube B 2023 "Under Pressure" - How fungi evade, exploit, and modulate cells of the innate immune system. Semin Immunol 66, 101738 PubMed
Seelbinder B, Lohinai Z, Vazquez-Uribe R, Brunke S, Chen X, Mirhakkak M, Lopez-Escalera S, Dome B, Megyesfalvi Z,  Berta J, Galffy G,  Dulka  E, Wellejus  A, Weiss GJ,  Bauer  M, Hube  B, Sommer MOA, Panagiotou  G 2023 Candida expansion in the gut of lung cancer patients associates with an ecological signature that supports growth under dysbiotic conditions. Nat Commun 14, 2673 Nature Commun
Chao YY, Puhach A, Frieser D, Arunkumar M, Lehner L, Seeholzer T, Garcia-Lopez A, van der Wal M, Fibi-Smetana S, Dietschmann A, Sommermann T, Ćiković T, Taher L, Gresnigt MS, Vastert SJ, van Wijk F, Panagiotou G, Krappmann D, Groß O, Zielinski CE. 2023 Human TH17 cells engage gasdermin E pores to release IL-1α on NLRP3 inflammasome activation. Nat Immunol. 24(2):295-308 PubMed
Sonnberger J, Kasper L, Lange T, Brunke S, Hube B 2023 "We've got to get out"-Strategies of human pathogenic fungi to escape from phagocytes. Mol Microbiol PubMed
Allert S, Schulz D, Kämmer P, Großmann P, Wolf T, Schäuble S, Panagiotou G, Brunke S, Hube B 2022 From environmental adaptation to host survival: Attributes that mediate pathogenicity of Candida auris. Virulence 13: 191-214. PubMed
Alonso-Roman R, Last A, Mirhakkak MH, Spraque JL, Möller L, Großmann P, Graf K, Gratz R, Mogavero S, Vylkova S, Panagiotou G, Schäuble S, Hube B, Gresnigt MS 2022 Lactobacillus rhamnosus colonisation antagonizes Candida albicans by forcing metabolic adaptations that compromise pathogenicity. Nat. Commun. 13, 3192 Nat. Commun.
Pekmezovic M, Dietschmann A, Gresnigt MS 2022 Type I interferons during host–fungus interactions: Is antifungal immunity going viral? PLoS Pathog 18: e1010740 PloS Pathog
Sprague JL, Kasper L, Hube B 2022 From intestinal colonization to systemic infections: Candida albicans translocation and dissemination Gut Microbes 14 :2154548 PubMed
Moreno-Velásquez SD, Pérez JC 2021 Imaging and quantification of mRNA molecules at single-cell resolution in the human fungal pathogen Candida albicans. mSphere 6: e0041121 PubMed
Pekmezovic M, Hovhannisyan H, Gresnigt MS, Iracane E, Oliveira-Pacheco J, Siscar-Lewin S, Seemann E, Qualmann B, Kalkreuter T, Müller S, Kamradt T, Mogavero S, Brunke S, Butler G, Gabaldón T, Hube B 2021 Candida pathogens induce protective mitochondria-associated type I interferon signalling and a damage-driven response in vaginal epithelial cells. Nat Microbiol 6: 643-57 PubMed
Kämmer P, McNamara S, Wolf T, Conrad T, Allert S, Gerwien F, Hünniger K, Kurzai O, Guthke R, Hube B, Linde J, Brunke S 2021 Survival strategies of pathogenic Candida species in human blood show independent and specific adaptations. mBio 11: e02435-20 PubMed
Fischer J, Gresnigt MS, Werz O, Hube B, Garscha U 2021 Candida albicans-induced leukotriene biosynthesis in neutrophils is restricted to the hyphal morphology. FASEB J 35: e21820 PubMed
Mogavero S, Sauer FM, Brunke S, Allert S, Schulz D, Wisgott S, Jablonowski N, Elshafee O, Krüger T, Kniemeyer O, Brakhage AA, Naglik JR, Dolk E, Hube B 2021 Candidalysin delivery to the invasion pocket is critical for host epithelial damage induced by Candida albicans. Cell microbiol 23: e13378 PubMed
Ferreira-Gomes M, Wich M, Böde S, Hube B, Jacobsen ID, Jungnickel B 2021 B cell recognition of Candida albicans hyphae via TLR 2 promotes IgG1 and IL-6 Secretion for TH17 differentiation. Front Immunol 12: 698849 PubMed
Reuter-Weissenberger P, Meir J, Pérez JC 2021 A fungal transcription regulator of vacuolar function modulates Candida albicans interactions with host epithelial cells mBio 12: e0302021 PubMed
Pekmezovic M, Kaune AK, Austermeier S, Hitzler SUJ, Mogavero S, Hovhannisyan H, Gabaldón T, Gresnigt MS, Hube B 2021 Human albumin enhances the pathogenic potential of Candida glabrata on vaginal epithelial cells. PLoS Pathog 17: e101003 PubMed
Wich M, Greim S, Ferreira-Gomes M, Krüger T, Kniemeyer O, Brakhage AA, Jacobsen ID, Hube B, Jungnickel B 2021 Functionality of the human antibody response to Candida albicans. Virulence 12: 3137-48 PubMed
Radosa S, Sprague JL, Lau SH, Tóth R, Linde J, Krüger T, Sprenger M, Kasper L, Westermann M, Kniemeyer O, Hube B, Brakhage AA, Gácser A, Hillmann F 2021 The fungivorous amoeba Protostelium aurantium targets redox homeostasis and cell wall integrity during intracellular killing of Candida parapsilosis. Cell Microbiol. 23(11): e13389 PubMed
Alonso-Monge R, Gresnigt MS, Román E, Hube B, Pla J 2021 Candida albicans colonization of the gastrointestinal tract: A double-edged sword. PLoS Pathog.17(7):  e1009710 PubMed
Ruben S, Garbe E, Mogavero S, Albrecht-Eckardt D, Hellwig D, Häder A, Krüger T, Gerth K, Jacobsen ID, Elshafee O, Brunke S, Hünniger K, Kniemeyer O, Brakhage AA, Morschhäuser J, Hube B, Vylkova S, Kurzai O, Martin R 2020 Ahr1 and Tup1 contribute to the transcriptional control of virulence-associated genes in Candida albicans. mBio 11: e00206-20 PubMed
Seelbinder B, Chen J, Brunke S, Uribe RV, Meyer AC, de Oliveira Lino FS, Chan KF, Loos D, Imamovic L, Tsang CC, Lam RPK, Sridhar S, Kang K, Hube B, Woo PCY, Sommer MOA, Panagiotou G 2020 Antibiotics create a shift from mutualism to competition in human gut communities with a longer-lasting impact on fungi than bacteria. Microbiome 8: 133 Microbiome
Kämmer P, McNamara S, Wolf T, Conrad T, Allert S, Gerwien F, Hünniger K, Kurzai O, Guthke R, Hube B, Linde J, Brunke S 2020 Survival strategies of pathogenic Candida species in human blood show independent and specific adaptations. mBio 11: e02435-20 PubMed
Mirhakkak MH, Schäuble S, Klassert TE, Brunke S, Brandt P, Loos D, Uribe RV, Senne de Oliveira Lino F, Ni Y, Vylkova S, Slevogt H, Hube B, Weiss GJ, Sommer MOA, Panagiotou G 2020 Metabolic modeling predicts specific gut bacteria as key determinants for Candida albicans colonization levels. ISME J 15: 1257-70 PubMed
Fischer D, Gessner G, Fill TP, Barnett R, Tron K, Dornblut K, Kloss F, Stallforth P, Hube B, Heinemann SH, Hertweck C, Scherlach K, Brunke S 2019 Disruption of membrane integrity by the bacteria-derived antifungal jagaricin. Antimicrob Agents Chemother 63: e00707-19 PubMed
Pérez JC 2019 Candida albicans dwelling in the mammalian gut. Curr Opin Microbiol 52: 41-6 (Review) PubMed
Cottier F, Sherrington S, Cockerill S, del Olmo Toledo V, Kissane S, Tournu H, Orsini L, Palmer GE, Pérez JC, Hall RA 2019 Remasking of Candida albicans β-Glucan in response to environmental pH is regulated by quorum sensing. mBio 10: e02347-19 PubMed
Moreno-Velásquez SD, Tint SH, Del Olmo Toledo V, Torsin S, De S, Pérez JC 2019 The regulatory proteins Rtg1/3 govern Sphingolipid homeostasis in the human associated yeast Candida albicans. Cell Rep 30: 620-9 PubMed
Siscar-Lewin S, Hube B, Brunke S 2019 Antivirulence and avirulence genes in human pathogenic fungi. Virulence 10: 935-47 (Review) PubMed
Ho J, Yang X, Nikou SA, Kichik N, Donkin A, Ponde NO, Richardson JP, Gratacap RL, Archambault LS, Zwirner CP, Murciano C, Henley-Smith R, Thavaraj S, Tynan CJ, Gaffen SL, Hube B, Wheeler RT, Moyes DL, Naglik JR 2019 Candidalysin activates innate epithelial immune responses via epidermal growth factor receptor. Nat Commun 10: 2297 PubMed
Naglik JR, Gaffen SL, Hube B 2019 Candidalysin: discovery and function in Candida albicans infections. Curr Opin Microbiol 52: 100-9 (Review) PubMed
Maurer M, Gresnigt MS, Last A, Wollny T, Berlinghof F, Pospich R, Cseresnyes Z, Medyukhina A, Graf K, Gröger M, Raasch M, Siwczak F, Nietzsche S, Jacobsen ID, Figge MT, Hube B, Huber O, Mosig AS 2019 A three-dimensional immunocompetent intestine-on-chip model as in vitro platform for functional and microbial interaction studies. Biomaterials 220: 119396 PubMed
Swidergall M, Khalaji M, Solis NV, Moyes DL, Drummond RA, Hube B, Lionakis MS, Murdoch C, Filler SG, Naglik JR 2019 Candidalysin is required for neutrophil recruitment and virulence during systemic Candida albicans infection. J Infect Dis 220: 1477-88 PubMed
Pekmezovic M, Mogavero S, Naglik JR, Hube B 2019 Host-pathogen interactions during female genital tract infections. Trends Microbiol 27: 982-96 (Review) PubMeds
Bacher P, Hohnstein T, Beerbaum E, Röcker M, Kaufmann S, Brandt C, Röhmel J, Stervbo U, Nienen M, Babel N, Milleck J, Assenmacher M, Cornely OA, Heine G, Worm M, Creutz P, Tabeling C, Ruwwe-Glösenkamp C, Sander LE, Brunke S, Hube B, Blango M, Kniemeyer O, Brakhage AA, Schwarz C, Scheffold A 2019 Human anti-fungal Th17 immunity and pathology rely on cross-reactivity against Candida albicans. Cell 176: 1340-55 PubMed
Westman J, Hube B, Fairn GD 2019 Integrity under stress: Host membrane remodelling and damage by fungal pathogens. Cell Microbiol 21: e13016 (Review) PubMed
Gerwien F, Skrahina V, Kasper L, Hube B, Brunke S 2018 Metals in fungal virulence. FEMS Microbiol Rev 42: fux050 (Review) 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: 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 9: 4260 PubMed
Crawford AC, Lehtovirta-Morley LE, Alamir O, Niemiec MJ, Alawfi B, Alsarraf M, Skrahina V, Costa ACBP, Anderson A, Yellagunda S, Ballou ER, Hube B, Urban CF, Wilson D 2018 Biphasic zinc compartmentalisation in a human fungal pathogen. PLoS Pathog 14: e1007013 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 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 (Review) 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 2: 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
Naglik JR, König A, Hube B, Gaffen SL 2017 Candida albicans-epithelial interactions and induction of mucosal innate immunity. Curr Opin Microbiol 40: 104-12 (Review) 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: 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