Fungal-host-microbiota interactions

Candida albicans and Lactobacillus rhamnosus interacting on intestinal epithelial cells

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.

Staff

Raquel Alonso-Román
Mark S Gresnigt
Selene Mogavero
Marisa Valentine

Publications

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.
d'Enfert C, Kaune AK, Alaban LR, Chakraborty S, Cole N, Delavy M, Kosmala D, Marsaux B, Fróis-Martins R, Morelli M, Rosati D, Valentine M, Xie Z, Emritloll Y, Warn PA, Bequet F, Bougnoux ME, Bornes S, Gresnigt MS, Hube B, Jacobsen ID, Legrand M, Leibundgut-Landmann S, Manichanh C, Munro CA, Netea MG, Queiroz K, Roget K, Thomas V, Thoral C, Van den Abbeele P, Walker AW, Brown AJP (2021) The impact of the Fungus-Host-Microbiota interplay upon Candida albicans infections: current knowledge and new perspectives. FEMS Microbiol Rev 45(3), fuaa060. (Review)
Last A, Maurer M, Mosig AS, Gresnigt MS, Hube B (2021) In vitro infection models to study fungal-host interactions. FEMS Microbiol Rev , fuab005.
Mogavero S, Hube B (2021) Candida albicans Interaction with oral epithelial cells: Adhesion, invasion and damage assays. Methods Mol Biol 2260, 133-143.
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(10), e13378.
Papon N, Naglik JR, Hube B, Goldman GH (2021) Fungal pathogenesis: A new venom. Curr Biol 31(8), R391-R394.
Zhang S, Edwards TN, Mogavero S, Mathers AR, Hube B, Berman J, Bougnoux ME, D'Enfert C, Kaplan DH (2021) Adenosine triphosphate released by Candida albicans is associated with reduced skin infectivity. J Invest Dermatol 141(9), 2306-2310.
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. (Review)
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.
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.