Project C5

Influence of gut microbiota on Candida albicans colonization, host immune response and candidiasis

Increasing evidence suggests a critical role of the microbiota for development of infections, mediated by both direct interactions between microorganisms and indirectly by modulation of immune responses. We hypothesize that the balance between microbiota, C. albicans and the host defense mechanisms affects the development of disseminated candidiasis. C5 will therefore address the role of the microbiota for (i) colonization resistance towards C. albicans, (ii) immune responses during colonization and (iii) the role of microbiota for susceptibility to systemic candidiasis.

Therefore, we will use genetically identical mice from different breeding facilities that can be expected to harbor distinct microbiomes. The functional consequences of different microbiota composition will be initially assessed determining the colonization resistance of the mice to C. albicans. Based on this, the host response to C. albicans colonization will be analyzed in detail in mice with different microbiota composition to deduce to which extend the existing microbiota affects the immunological response to C. albicans. Furthermore, we will determine to which extent differences in microbiota composition affect the clinical outcome of translocation and systemic candidiasis. In parallel microbiome and mycobiota analysis will be performed in human patients to analyze if patterns observed in mice are transferable to human patients.

Influence of the microbiome on colonization resistance and host response.
Influence of the microbiome on colonization resistance and host response.
Principal Investigators
Prof. Dr. Michael Bauer
Prof. Dr. Michael Bauer

Clinic of Anaesthesiology and Intensive Care Medicine

University Hospital Jena

michael.bauer@med.uni-jena.de

Prof. Dr. Ilse D. Jacobsen
Prof. Dr. Ilse D. Jacobsen

Research Group Microbial Immunology

Leibniz Institute for Natural Product Research and Infection Biology – Hans Knöll Institute  

ilse.jacobsen@leibniz-hki.de

Publications
Author Year Title Journal Links
Schaarschmidt B, Vlaic S, Medyukhina A, Neugebauer S, Nietzsche S, Gonnert FA, Rödel J, Singer M, Kiehntopf M, Figge MT, Jacobsen ID, Bauer M, Press AT 2018 Molecular signatures of liver dysfunction are distinct in fungal and bacterial infections in mice. Theranostics 8: 3766-80  
Irmscher S, Döring N, Halder LD, Jo EAH, Kopka I, Dunker C, Jacobsen ID, Luo S, Slevogt H, Lorkowski S, Beyersdorf N, Zipfel PF, Skerka C 2018 Kallikrein cleaves C3 and activates complement. J Innate Immun 10: 94-105 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
Conrad T, Kniemeyer O, Henkel SG, Krüger T, Mattern DJ, Valiante V, Guthke R, Jacobsen ID, Brakhage AA, Vlaic S, Linde J 2018 Module-detection approaches for the integration of multilevel omics data highlight the comprehensive response of Aspergillus fumigatus to caspofungi. BMC Syst Biol 12:88 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
Halder LD, Abdelfatah MA, Jo E, Jacobsen ID, Westermann M, Beyersdorf N, Lorkowski S, Zipfel PF, Skerka C 2017 Factor H binds to extracellular DNA traps released from human blood monocytes in response to Candida albicans. Front Immunol 7: 671 PubMed
Schulze B, Rambach G, Schwartze VU, Voigt K, Schubert K, Speth C, Jacobsen ID 2017 Ketoacidosis alone does not predispose to mucormycosis by Lichtheimia in a murine pulmonary infection model. Virulence 8: 1657-67 PubMed
Jacobsen ID, Hube B 2017 Candida albicans morphology: still in focus. Expert Rev Anti Infect Ther 15: 327-30 (Editorial) PubMed
Kroll K, Shekhova E, Mattern DJ, Thywissen A, Jacobsen ID, Strassburger M, Heinekamp T, Shelest E, Brakhage AA, Kniemeyer O 2016 The hypoxia-induced dehydrogenase HorA is required for coenzyme Q10 biosynthesis, azole sensitivity and virulence of Aspergillus fumigatus. Mol Microbiol 101: 92-108 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
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
Duggan S, Essig F, Hünniger K, Mokhtari Z, Bauer L, Lehnert T, Brandes S, Häder A, Jacobsen ID, Martin R, Figge MT, Kurzai O 2015 Neutrophil activation by Candida glabrata but not Candida albicans promotes fungal uptake by monocytes. Cell Microbiol 17: 1259-76 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
Schwartze VU, Santiago AL, Jacobsen ID, Voigt K 2014 The pathogenic potential of the Lichtheimia genus revisited: Lichtheimia brasiliensis is a novel, non-pathogenic species. Mycoses 57 Suppl 3: 128-31 PubMed