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.
Principal Investigators
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
Publications
| Author | Year | Title | Journal | Links |
|---|---|---|---|---|
| Schaefer S, Vij R, Sprague JL, Austermeier S, Dinh H, Judzewitsch PR, Müller-Loennies S, Lopes Silva T, Seemann E, Qualmann B, Hertweck C, Scherlach K, Gutsmann T, Cain AK, Corrigan N, Gresnigt MS, Boyer C, Lenardon MD, Brunke S | 2024 | A synthetic peptide mimic kills Candida albicans and synergistically prevents infection. | Nat Commun. 15(1):6818 | PubMed |
| 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 |
| Valentine M, Rudolph P, Dietschmann A, Tsavou A, Mogavero S, Lee S, Priest EL, Zhurgenbayeva G, Jablonowski N, Timme S, Eggeling C, Allert S, Dolk E, Naglik JR, Figge MT, Gresnigt MS, Hube B | 2024 | Nanobody-mediated neutralization of candidalysin prevents epithelial damage and inflammatory responses that drive vulvovaginal candidiasis pathogenesis | mBio:e0340923 | PubMed |
| Müller R, König A, Groth S, Zarnowski R, Visser C, Handrianz T, Maufrais C, Krüger T, Himmel M, Lee S, Priest EL, Yildirim D, Richardson JP, Blango MG, Bougnoux ME, Kniemeyer O, d'Enfert C, Brakhage AA, Andes DR, Trümper V, Nehls C, Kasper L, Mogavero S, Gutsmann T, Naglik JR, Allert S, Hube B | 2024 | Secretion of the fungal toxin candidalysin is dependent on conserved precursor peptide sequences. | Nat Microbiol. (3):669-683. | PubMed |
| Sprague JL, Schille TB, Allert S, Trümper V, Lier A, Großmann P, Priest EL, Tsavou A, Panagiotou G, Naglik JR, Wilson D, Schäuble S, Kasper L, Hube B | 2024 | Candida albicans translocation through the intestinal epithelial barrier is promoted by fungal zinc acquisition and limited by NFκB-mediated barrier protection. | PLoS Pathog. 20(3):e1012031 | PubMed |
| Kaden T, Alonso-Roman R, Akbarimoghaddam P, Mosig AS, Graf K, Raasch M, Hoffmann B, Figge MT, Hube B, Gresnigt MS | 2024 | Modeling of intravenous caspofungin administration using an intestine-on-chip reveals altered Candida albicans microcolonies and pathogenicity. | Biomaterials. 9;307:122525 | PubMed |
| Alonso-Roman R, Mosig AS, Figge MT , Papenfort K, Eggeling Ch, Schachter FH, Hube B, Gresnigt MS | 2024 | Organ-on-chip models for infectious disease research. | Nat Microbiol 9, 891–904 | nature microbiology |
| 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 |