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
Publications
Author Year Title Journal Links
Halder LD, Babych S, Palme DI, Mansouri-Ghahnavieh E, Ivanov L, Ashonibare V, Langenhorst D, Prusty B, Rambach G, Wich M, Trinks N, Blango MG, Kornitzer D, Terpitz U, Speth C, Jungnickel B, Beyersdorf N, Zipfel PF, Brakhage AA, Skerka C 2022 Candida albicans induces cross-kingdom miRNA trafficking in human monocytes to promote fungal growth. mBio 13(1): e0356321 mBio
Ramírez-Zavala B, Krüger I, Dunker C, Jacobsen ID, Morschhäuser J 2022 The protein kinase Ire1 has a Hac1-independent essential role in iron uptake and virulence of Candida albicans. PLoS Pathog 18(2): e1010283 PubMed
Niemiec MJ, Kapitan M, Himmel M, Döll K, Krüger T, Köllner TG, Auge I, Kage F, Alteri CJ, Mobley HLT, Monsen T, Linde S, Nietzsche S, Kniemeyer O, Brakhage AA, Jacobsen ID 2022 Augmented Enterocyte Damage During Candida albicans and Proteus mirabilis Coinfection. Front Cell Infect Microbiol. 12:866416 PubMed
Machata S, Sreekantapuram S, Hünniger K, Kurzai O, Dunker C, Schubert K, Krüger W, Schulze-Richter B, Speth C, Rambach G, Jacobsen ID 2021 Significant differences in host-pathogen interactions between murine and human whole blood. Front Immunol 11: 3489 Frontiers
Dunker C, Polke M, Schulze-Richter B, Schubert K, Rudolphi S, Gressler AE, Pawlik T, Prada Salcedo JP, Niemiec MJ, Slesiona-Künzel S, Swidergall M, Martin R, Dandekar T, Jacobsen ID 2021 Rapid proliferation due to better metabolic adaptation results in full virulence of a filament-deficient Candida albicans strain. Nat Commun 12: 3899 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
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
Böttcher K, Braunschmidt K, Hirth G, Schärich K, Klassert TE, Stock M, Sorgatz J, Fischer-Burkart S, Ullrich S, Frankenberger S, Kritsch D, Kosan C, Küppers R, Strobl LJ, Slevogt H, Zimber-Strobl U, Jungnickel B 2021 Context-dependent regulation of immunoglobulin mutagenesis by p53. Molecular Immunology 138: 128–136 PubMed
Halder LD, Jo EAH, Hasan MZ, Ferreira-Gomes M, Krüger T, Westermann M, Palme DI, Rambach G, Beyersdorf N, Speth C, Jacobsen ID, Kniemeyer O, Jungnickel B, Zipfel PF, Skerka C 2020 Immune modulation by complement receptor 3 dependent human monocyte TGF-β1-transporting vesicles. Nat Commun 11: 2331 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
Gerwien F, Dunker C, Brandt P, Garbe E, Jacobsen ID, Vylkova S 2020 Clinical Candida albicans vaginal isolates and a laboratory strain show divergent behaviors during macrophage interactions. mSphere 5: e00393-20 PubMed
Arend N, Pittner A, Ramoji A, Mondol AS, Dahms M, Rüger J, Kurzai O, Schie IW, Bauer M, Popp J, Neugebauer U 2020 Detection and differentiation of bacterial and fungal Infection of neutrophils from peripheral blood using raman spectroscopy. Anal Chem 92: 10560-8 PubMed
Machata S, Müller MM, Lehmann R, Sieber S, Panagiotou G, Carvalho A, Cunha C, Lagrou K, Maertens J, Slevogt H, Jacobsen ID 2020 Proteome analysis of bronchoalveolar lavage fluids reveals host and fungal proteins highly expressed during invasive pulmonary aspergillosis in mice and humans. Virulence 11: 1337-51 Virulence
Khaliq W, Großmann P, Neugebauer S, Kleyman A, Domizi R, Calcinaro S, Brealey D, Gräler M, Kiehntopf M, Schäuble S, Singer M, Panagiotou G, Bauer M 2020 Lipid metabolic signatures deviate in sepsis survivors compared to non-survivors. Comput Struct Biotechnol J 18: 3678-3691 Science direct
Matthias J, Heink S, Picard F, Zeiträg J, Kolz A, Chao YY, Soll D, de Almeida GP, Glasmacher E, Jacobsen ID, Riedel T, Peters A, Floess S, Huehn J, Baumjohann D, Huber M, Korn T, Zielinski CE 2020 Salt generates antiinflammatory Th17 cells but amplifies pathogenicity in proinflammatory cytokine microenvironments. J Clin Invest 130: 4587-600 PubMed
von Müller C, Bulman F, Wagner L, Rosenberger D, Marolda A, Kurzai O, Eißmann P, Jacobsen ID, Perner B, Hemmerich P, Vylkova S 2020 Active neutrophil responses counteract Candida albicans burn wound infection of ex vivo human skin explants. Sci Rep 10: 21818 PubMed
Krüger W, Vielreicher S, Kapitan M, Jacobsen ID, Niemiec MJ 2019 Fungal-bacterial interactions in health and disease. Pathogens 8: 70 (Review) PubMed
Klaile E, Müller MM, Brehme S, Zubiria-Barrera C, Klassert TE, Stock M, Durotin A, Nguyen TD, Feer S, Singer BB, Zipfel PF, Rudolphi S, Jacobsen ID, Slevogt H 2019 Unaltered fungal burden and lethality in human CEACAM1-transgenic mice during Candida albicans dissemination and systemic infection. Front Microbiol 10: 2703 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
Polke M, Leonhardt I, Kurzai O, Jacobsen ID 2018 Farnesol signalling in Candida albicans - more than just communication. Crit Rev Microbiol 44: 230-43 (Review) PubMed
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 PubMed
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 caspofungin. BMC Syst Biol 12: 88 PubMed
Luo S, Dasari P, Reiher N, Hartmann A, Jacksch S, Wende E, Barz D, Niemiec MJ, Jacobsen I, Beyersdorf N, Hünig T, Klos A, Skerka C, Zipfel PF 2018 The secreted Candida albicans protein Pra1 disrupts host defense by broadly targeting and blocking complement C3 and C3 activation fragments. Mol Immunol 93: 266-77 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