In vitro infection models with physiological relevance

In vitro infection models are essential for the study of fungal infection biology. However, it remains difficult to fully recapitulate the physiological host niches using in vitro models.For example, the bacterial microbiota is essential in preventing C. albicans infections since antibiotic therapy is a major predisposing factor for common mucosal as well as systemic candidiasis.

In close collaboration with the Department of Microbial Pathogenicity Mechanisms we develop and use novel in vitro models in which physiological attributes are simulated. These models range from in vitro cell culture models that integrate commensal bacteria to dynamic Organ-on-Chip models that recapitulate the epithelial barrier, the bloodstream, the innate immune system, and bacterial colonization of the epithelia. The Organ-on-Chip models have been adapted as Candida infection models in collaboration with the University Clinic Jena (UKJ) group INSPIRE.

We use these models to investigate the influence of specific host and microbiota factors and the interplay between the bacterial microbiota and C. albicans. Specifically, we investigate the mechanisms imposed by the microbiota and host that tip the balance between the commensal nature of C. albicans and pathogenicity. These projects are in collaboration with the Department of Microbial Pathogenicity Mechanisms within the framework of the Marie Currie International Training Network FunHoMic and the Cluster of Excellence Balance of the Microverse.

Staff

Raquel Alonso-Román
Mark S Gresnigt
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.
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)
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.
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.

Funding