期刊
DISEASE MODELS & MECHANISMS
卷 12, 期 9, 页码 -出版社
COMPANY BIOLOGISTS LTD
DOI: 10.1242/dmm.039719
关键词
Candida albicans; Microbiota; Commensalism; Lactobacilli; Antagonism; In vitro model
资金
- European Union [812969, 812954]
- Center for Sepsis Control and Care (CSCC)/Bundesministerium fur Bildung und Forschung (BMBF) [01EO1002]
- Infect ERA-NET Program (FunComPath
- BMBF grant) [031L0001A]
- Humboldt Research Fellowship (Alexander von Humboldt-Stiftung)
- Marie Curie Actions (MSCA) [812969] Funding Source: Marie Curie Actions (MSCA)
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.
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