From commensalism to pathogenesis

From commensalism to pathogenesis
From commensalism to pathogenesis

The gut is believed to be the main reservoir of Candida albicans, where the fungus lives as a harmless commensal, in a peaceful cohabitation with “the good” bacteria. However, C. albicans can invade this tissue and enter the bloodstream (translocation) due to alterations of the gut’s physiology. A major risk factor is the use of antibiotics. In fact, it has been shown that the removal of protective bacteria from the gut is a prerequisite for the translocation of the fungus into the bloodstream. From here, the fungus can infect almost all organs and finally cause sepsis. Our aim is to elucidate which factors (of the fungus as well as of the host) are responsible for the shift of C. albicans to a pathogenic state.

We are using genome-wide transcription profiling techniques on in vitro (translocation and damage of host cells), ex vivo (perfused gut) and in vivo (mouse) infection models for translocation. Genes associated with colonization or translocation will be analyzed in detail with a focus on those with previously unknown function.

Another aspect which will be studied in detail is the shift from commensalism to a pathogenic state, by establishing a commensal gut model, where C. albicans grows in equilibrium with protective probiotic bacteria on intestinal epithelial tissue. 

Publications

Bacher P, Hohnstein T, Beerbaum E, Röcker M, Blango MG, Kaufmann S, Röhmel J, Eschenhagen P, Grehn C, Seidel K, Rickerts V, Lozza L, Stervbo U, Nienen M, Babel N, Milleck J, Assenmacher M, Cornely OA, Ziegler M, Wisplinghoff H, Heine G, Worm M, Siegmund B, Maul J, Creutz P, Tabeling C, Ruwwe-Glösenkamp C, Sander LE, Knosalla C, Brunke S, Hube B, 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(6), 1340-1355.e15. Details PubMed

Domínguez-Andrés J, Novakovic B, Li Y, Scicluna BP, Gresnigt MS, Arts RJW, Oosting M, Moorlag SJCFM, Groh LA, Zwaag J, Koch RM, Ter Horst R, Joosten LAB, Wijmenga C, Michelucci A, van der Poll T, Kox M, Pickkers P, Kumar V, Stunnenberg H, Netea MG (2019) The Itaconate Pathway Is a Central Regulatory Node Linking Innate Immune Tolerance and Trained Immunity. Cell Metab [Accepted] Details PubMed

Drummond RA, Swamydas M, Oikonomou V, Zhai B, Dambuza IM, Schaefer BC, Bohrer AC, Mayer-Barber KD, Lira SA, Iwakura Y, Filler SG, Brown GD, Hube B, Naglik JR, Hohl TM, Lionakis MS (2019) CARD9+ microglia promote antifungal immunity via IL-1β- and CXCL1-mediated neutrophil recruitment. Nat Immunol 20(5), 559-570. Details 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 , Details PubMed

Gabaldón T (2019) Recent trends in molecular diagnostics of yeast infections: from PCR to NGS. FEMS Microbiol Rev , Details PubMed

Graf K, Last A, Gratz R, Allert S, Linde S, Westermann M, Gröger M, Mosig AS, Gresnigt MS, Hube B (2019) Keeping Candida commensal - How lactobacilli antagonize pathogenicity of Candida albicans in an in vitro gut model. Dis Model Mech , Details PubMed

Grondman I, Arts RJW, Koch RM, Leijte GP, Gerretsen J, Bruse N, Kempkes RWM, Ter Horst R, Kox M, Pickkers P, Netea MG, Gresnigt MS (2019) Frontline Science: Endotoxin-induced immunotolerance is associated with loss of monocyte metabolic plasticity and reduction of oxidative burst. J Leukoc Biol [Accepted] Details 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(1), 2297. Details PubMed

Ishchuk OP, Ahmad KM, Koruza K, Bojanovič K, Sprenger M, Kasper L, Brunke S, Hube B, Säll T, Hellmark T, Gullstrand B, Brion C, Freel K, Schacherer J, Regenberg B, Knecht W, Piškur J (2019) RNAi as a Tool to Study Virulence in the Pathogenic Yeast Candida glabrata. Front Microbiol 10, 1679. Details PubMed

Jaeger M, Matzaraki V, Aguirre-Gamboa R, Gresnigt MS, Chu X, Johnson MD, Oosting M, Smeekens SP, Withoff S, Jonkers I, Perfect JR, van de Veerdonk FL, Kullberg BJ, Joosten LAB, Li Y, Wijmenga C, Netea MG, Kumar V (2019) A Genome-Wide Functional Genomics Approach Identifies Susceptibility Pathways to Fungal Bloodstream Infection in Humans. J Infect Dis [Accepted] Details PubMed

Jaeger M, Pinelli M, Borghi M, Constantini C, Dindo M, van Emst L, Puccetti M, Pariano M, Ricaño-Ponce I, Büll C, Gresnigt MS, Wang X, Gutierrez Achury J, Jacobs CWM, Xu N, Oosting M, Arts P, Joosten LAB, van de Veerdonk FL, Veltman JA, Ten Oever J, Kullberg BJ, Feng M, Adema GJ, Wijmenga C, Kumar V, Sobel J, Gilissen C, Romani L, Netea MG (2019) A systems genomics approach identifies SIGLEC15 as a susceptibility factor in recurrent vulvovaginal candidiasis. Sci Transl Med [Accepted] Details PubMed

Naglik JR, Gaffen SL, Hube B (2019) Candidalysin: discovery and function in Candida albicans infections. Curr Opin Microbiol 52, 100-109. Details PubMed

Pekmezovic M, Mogavero S, Naglik JR, Hube B (2019) Host-Pathogen Interactions during Female Genital Tract Infections. Trends Microbiol , Details PubMed

Swidergall M, Khalaji M, Solis N, Moyes D, Drummond R, Hube B, Lionakis M, Murdoch C, Filler S, Naglik J (2019) Candidalysin is required for neutrophil recruitment and virulence during systemic Candida albicans infection Journal of Infectious Diseases , Details

Allert S*, Förster TM*, Svensson C-M, 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(3), e00915-18. Details PubMed Open Access

Assendorp EL, Gresnigt MS, Sprenkeler EGG, Meis JF, Dors N, van der Linden JWM, Henriet SSV (2018) Adjunctive interferon-γ immunotherapy in a pediatric case of Aspergillus terreus infection. Eur J Clin Microbiol Infect Dis [Accepted] Details PubMed

Engel M, Kasper L, Barmet C, Schmid T, Vionnet L, Wilm B, Pruessmann KP (2018) Single-shot spiral imaging at 7 T. Magn Reson Med [Accepted] Details PubMed

Frässle S, Lomakina EI, Kasper L, Manjaly ZM, Leff A, Pruessmann KP, Buhmann JM, Stephan KE (2018) A generative model of whole-brain effective connectivity. Neuroimage [Accepted] Details PubMed

Kachamakova-Trojanowska N, Jazwa-Kusior A, Szade K, Kasper L, Soja J, Andrychiewicz A, Jakiela B, Plutecka H, Sanak M, Jozkowicz A, Sladek K, Dulak J (2018) Molecular profiling of regulatory T cells in pulmonary sarcoidosis. J Autoimmun [Accepted] Details PubMed

Kasper L, Engel M, Barmet C, Haeberlin M, Wilm BJ, Dietrich BE, Schmid T, Gross S, Brunner DO, Stephan KE, Pruessmann KP (2018) Rapid anatomical brain imaging using spiral acquisition and an expanded signal model. Neuroimage [Accepted] Details PubMed

Moock P, Kasper L, Jäger M, Stolarek D, Richter H, Bruns J, Petermann K (2018) TDM-controlled ring resonator arrays for fast, fixed-wavelength optical biosensing. Opt Express [Accepted] Details PubMed

Wirthmann AE, Majenka P, Kaufmann MC, Wellenbrock SV, Kasper L, Hüttinger S, Djedovic G, Bozkurt A, Sohn M, Rieger UM (2018) Phalloplasty in Female-to-Male Transsexuals by Gottlieb and Levine's Free Radial Forearm Flap Technique-A Long-Term Single-Center Experience Over More than Two Decades. J Reconstr Microsurg [Accepted] Details PubMed

Wirthmann AE, Welsch L, Wellenbrock SV, Kasper L, Schlosshauer T, Bozkurt A, Hüttinger S, Rieger UM (2018) Reduction mammoplasty in adolescents and elderly: A ten year case series analyzing age related outcome with focus on safety and complications. J Plast Reconstr Aesthet Surg [Accepted] Details PubMed

Wolf T, Kämmer P, Brunke S, Linde J (2018) Two's company: studying interspecies relationships with dual RNA-seq. Curr Opin Microbiol 42, 7-12. (Review) Details PubMed Open Access

Hsieh SH, Brunke S, Brock M (2017) Encapsulation of antifungals in micelles protects Candida albicans during gall-bladder infection. Front Microbiol 8, 117. Details PubMed Open Access

Köhler JR, Hube B, Puccia R, Casadevall A, Perfect JR (2017) Fungi that infect humans. Microbiol Spectr 5(3), FUNK-0014-2016. (Review) Details PubMed

Mailänder-Sánchez D, Braunsdorf C, Grumaz C, Müller C, Lorenz S, Stevens P, Wagener J, Hebecker B, Hube B, Bracher F, Sohn K, Schaller M (2017) Antifungal defense of probiotic Lactobacillus rhamnosus GG is mediated by blocking adhesion and nutrient depletion. PLOS ONE 12(10), e0184438. Details PubMed Open Access

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(6), 989-1007. Details 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(12), 1709-1715. (Review) Details 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. Details PubMed Open Access PDF

Jakab Á, Mogavero S, Förster TM, Pekmezovic M, Jablonowski N, Dombrádi V, Pócsi I, Hube B (2016) Effects of the glucocorticoid betamethasone on the interaction of Candida albicans with human epithelial cells. Microbiology 162(12), 2116-2125. Details PubMed

Whittington A, Gow NAR, Hube B (2014) From commensal to pathogen: Candida albicans. In: Esser K, Kurzai O (eds.) The Mycota Ed. 2. Vol. XII, pp. 3-18. Springer Verlag. Details

Gow NA, Hube B (2012) Importance of the Candida albicans cell wall during commensalism and infection. Curr Opin Microbiol 15(4), 406-412. (Review) Details PubMed

Wächtler B, Citiulo F, Jablonowski N, Förster S, Dalle F, Schaller M, Wilson D, Hube B (2012) Candida albicans-epithelial interactions: dissecting the roles of active penetration, induced endocytosis and host factors on the infection process. PLOS One 7(5), e36952. Details PubMed

Dalle F, Wächtler B, L'Ollivier C, Holland G, Bannert N, Wilson D, Labruère C, Bonnin A, Hube B (2010) Cellular interactions of Candida albicans with human oral epithelial cells and enterocytes. Cell Microbiol 12(2), 248-271. Details PubMed

Wilson D, Thewes S, Zakikhany K, Fradin C, Albrecht A, Almeida R, Brunke S, Grosse K, Martin R, Mayer F, Leonhardt I, Schild L, Seider K, Skibbe M, Slesiona S, Waechtler B, Jacobsen I, Hube B (2009) Identifying infection-associated genes of Candida albicans in the postgenomic era. FEMS Yeast Res 9(5), 688-700. (Review) Details PubMed

Hube B (2004) From commensal to pathogen: stage- and tissue-specific gene expression of Candida albicans. Curr Opin Microbiol 7(4), 336-341. (Review) Details PubMed

Staff

Dr. Stefanie Allert

Phone: +49 3641 532-1141 Email: stefanie.allert@leibniz-hki.de

Sophie Austermeier

Phone: +49 3641 532-1389 Email: sophie.austermeier@leibniz-hki.de

Osama Elshafee

Phone: +49 3641 532-1225 Email: osama.elshafee@leibniz-hki.de

Dr. Mark Sebastiaan Gresnigt

Phone: +49 3641 532-1305 Email: mark.gresnigt@leibniz-hki.de

Dr. Lydia Kasper

Phone: +49 3641 532-1219 Email: lydia.kasper@leibniz-hki.de

Antonia Last

Phone: +49 3641 532-1595 Email: antonia.last@leibniz-hki.de

Dr. Selene Mogavero

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Jakob Sprague

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Marisa Valentine

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