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Dis Model Mech. 2019 Sep 12;12(9). pii: dmm039719. doi: 10.1242/dmm.039719.

Keeping Candida commensal: how lactobacilli antagonize pathogenicity of Candida albicans in an in vitro gut model.

Author information

1
Department of Microbial Pathogenicity Mechanisms, Leibniz Institute for Natural Product Research and Infection Biology-Hans-Knoell-Institute, Beutenbergstraße 11A, 07745 Jena, Germany.
2
Center for Electron Microscopy Jena University Hospital, Ziegelmühlenweg 1, 07743 Jena, Germany.
3
Center for Sepsis Control and Care (CSCC), University Hospital Jena, Am Klinikum 1, 07747 Jena, Germany.
4
Institute of Biochemistry II, Jena University Hospital, Am Klinikum 1, 07747 Jena, Germany.
5
Department of Microbial Pathogenicity Mechanisms, Leibniz Institute for Natural Product Research and Infection Biology-Hans-Knoell-Institute, Beutenbergstraße 11A, 07745 Jena, Germany bernhard.hube@hki-jena.de.
6
Friedrich Schiller University, Fürstengraben 1, 07743 Jena, Germany.

Abstract

The intestine is the primary reservoir of Candida albicans that can cause systemic infections in immunocompromised patients. In this reservoir, the fungus exists as a harmless commensal. However, antibiotic treatment can disturb the bacterial microbiota, facilitating fungal overgrowth and favoring pathogenicity. The current in vitro gut models that are used to study the pathogenesis of C. albicans investigate the state in which C. albicans behaves as a pathogen rather than as a commensal. We present a novel in vitro gut model in which the fungal pathogenicity is reduced to a minimum by increasing the biological complexity. In this model, enterocytes represent the epithelial barrier and goblet cells limit C. albicans adhesion and invasion. Significant protection against C. albicans-induced necrotic damage was achieved by the introduction of a microbiota of antagonistic lactobacilli. We demonstrated a time-, dose- and species-dependent protective effect against C. albicans-induced cytotoxicity. This required bacterial growth, which relied on the presence of host cells, but was not dependent on the competition for adhesion sites. Lactobacillus rhamnosus reduced hyphal elongation, a key virulence attribute. Furthermore, bacterial-driven shedding of hyphae from the epithelial surface, associated with apoptotic epithelial cells, was identified as a main and novel mechanism of damage protection. However, host cell apoptosis was not the driving mechanism behind shedding. Collectively, we established an in vitro gut model that can be used to experimentally dissect commensal-like interactions of C. albicans with a bacterial microbiota and the host epithelial barrier. We also discovered fungal shedding as a novel mechanism by which bacteria contribute to the protection of epithelial surfaces.This article has an associated First Person interview with the joint first authors of the paper.

KEYWORDS:

Antagonism; Candida albicans; Commensalism; In vitro model; Lactobacilli; Microbiota

PMID:
31413153
DOI:
10.1242/dmm.039719
Free PMC Article

Conflict of interest statement

Competing interestsThe authors declare no competing or financial interests.

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