Dataset Information

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

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.

SUBMITTER: Graf K

PROVIDER: S-EPMC6765188 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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

Graf Katja K Last Antonia A Gratz Rena R Allert Stefanie S Linde Susanne S Westermann Martin M Gröger Marko M Mosig Alexander S AS Gresnigt Mark S MS Hube Bernhard B

Disease models & mechanisms 20190912 9

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 ...[more]

PMID: 31413153

Similar Datasets

Project description:Biofilm-associated polymicrobial infections, particularly those involving fungi and bacteria, are responsible for significant morbidity and mortality and tend to be challenging to treat. Candida albicans and Staphylococcus aureus specifically are considered leading opportunistic fungal and bacterial pathogens, respectively, mainly due to their ability to form biofilms on catheters and indwelling medical devices. However, the impact of mixed-species biofilm growth on therapy remains largely understudied. In this study, we investigated the influence of C. albicans secreted cell wall polysaccharides on the response of S. aureus to antibacterial agents in biofilm. Results demonstrated significantly enhanced tolerance for S. aureus to drugs in the presence of C. albicans or its secreted cell wall polysaccharide material. Fluorescence confocal time-lapse microscopy revealed impairment of drug diffusion through the mixed biofilm matrix. Using C. albicans mutant strains with modulated cell wall polysaccharide expression, exogenous supplementation, and enzymatic degradation, the C. albicans-secreted ?-1,3-glucan cell wall component was identified as the key matrix constituent providing the bacteria with enhanced drug tolerance. Further, antibody labeling demonstrated rapid coating of the bacteria by the C. albicans matrix material. Importantly, via its effect on the fungal biofilm matrix, the antifungal caspofungin sensitized the bacteria to the drugs. Understanding such symbiotic interactions with clinical relevance between microbial species in biofilms will greatly aid in overcoming the limitations of current therapies and in defining potential new targets for treating polymicrobial infections.The fungus Candida albicans and the bacterium Staphylococcus aureus are important microbial pathogens responsible for the majority of infections in hospitalized patients and are often coisolated from a host. In this study, we demonstrated that when grown together, the fungus provides the bacterium with enhanced tolerance to antimicrobial drugs. This process was mediated by polysaccharides secreted by the fungal cell into the environment. The biofilm matrix formed by these polysaccharides prevented penetration by the drugs and provided the bacteria with protection. Importantly, we show that by inhibiting the production of the fungal polysaccharides, a specific antifungal agent indirectly sensitized the bacteria to antimicrobials. Understanding the therapeutic implications of the interactions between these two diverse microbial species will aid in overcoming the limitations of current therapies and in defining new targets for treating complex polymicrobial infections.

Dataset Information

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

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets