Fungal-host-microbiota interactions

Candida albicans is a regular member of the intestinal microbiota in the majority of the human population, but can also colonize the oral or vaginal mucosa. In such environments this yeast lives as a harmless commensal in cohabitation with the bacterial microbiota without inducing competitive interactions or immune responses detrimental to its survival. However, specific conditions such as a dysbalanced microbiome, suppression of the immune system, and an impaired epithelial barrier function can predispose for oral or vulvovaginal infections or even invasive, mostly nosocomial, C. albicans infections.

In particular, the association between the use of antibiotics and C. albicans infection illustrates that bacterial microbiota is crucial in preventing fungal pathogenesis. Furthermore, murine models and patient studies demonstrate that removal of protective bacteria is a major predisposing factor favoring a commensal-to-pathogen shift and initiation of disease.

We are investigating bacteria that antagonize the pathogenicity of C. albicans and which may contribute to keeping this opportunistic pathogen in a commensal state. We use genome-wide transcription profiling techniques, metabolomics, and state-of-the-art in vitro infection models to uncover the molecular interactions between C. albicans and bacteria that antagonize its pathogenicity. Using organ-on-chip models that integrate epithelial cells, immune cells, and a bloodstream-like compartment, the three-way interaction between the fungus, host, and members of the bacterial microbiota is investigated. We also closely collaborate with the Junior Research Group Adaptive Pathogenicity Strategies on how these interactions influence immune recognition.

Also, recently, it has been described that the bacterial Type 6 Secretion System (T6SS), such as the one from the bacterium Serratia marcescens, can directly act against fungi. This might have a key role in determining the fate of a fungal infection. We just started investigating how anti-fungal T6SS can influence the nature and outcome of a bacterial-fungal co-colonization or co-infection of the mammalian gut.

Publications

Kumamoto CA, Gresnigt MS, Hube B (2020) The gut, the bad and the harmless: Candida Albicans as a commensal and opportunistic pathogen in the intestine. Curr Opin Microbiol 56, 7-15. 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 63(9), e00707-19. Details PubMed Open Access PDF

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 12(9), dmm039719. Details PubMed Open Access PDF

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. Details PubMed

Brunke S, Hube B (2018) The needle and the damage done. Nat Microbiol 3(8), 860-861. (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

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

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

Staff

Raquel Alonso-Román

Phone: +49 3641 532-1157 Email: raquel.roman@leibniz-hki.de

Dr. Mark S Gresnigt

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

Antonia Last

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

Dr. Selene Mogavero

Phone: +49 3641 532-1568 Email: selene.mogavero@leibniz-hki.de

Marisa Valentine

Phone: +49 3641 532-1159 Email: marisa.valentine@leibniz-hki.de