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Augmented enterocyte damage during Candida albicans and Proteus mirabilis coinfection
Leibniz Institute for Natural Product Research and Infection Biology – Hans Knöll Institute, Jena, Germany; Center for Sepsis Control and Care, Jena, Germany.
Leibniz Institute for Natural Product Research and Infection Biology – Hans Knöll Institute, Jena, Germany; Center for Sepsis Control and Care, Jena, Germany.
Leibniz Institute for Natural Product Research and Infection Biology – Hans Knöll Institute, Jena, Germany.
Leibniz Institute for Natural Product Research and Infection Biology – Hans Knöll Institute, Jena, Germany.
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2022 (English)In: Frontiers in Cellular and Infection Microbiology, E-ISSN 2235-2988, Vol. 12, article id 866416Article in journal (Refereed) Published
Abstract [en]

The human gut acts as the main reservoir of microbes and a relevant source of life-threatening infections, especially in immunocompromised patients. There, the opportunistic fungal pathogen Candida albicans adapts to the host environment and additionally interacts with residing bacteria. We investigated fungal-bacterial interactions by coinfecting enterocytes with the yeast Candida albicans and the Gram-negative bacterium Proteus mirabilis resulting in enhanced host cell damage. This synergistic effect was conserved across different P. mirabilis isolates and occurred also with non-albicans Candida species and C. albicans mutants defective in filamentation or candidalysin production. Using bacterial deletion mutants, we identified the P. mirabilis hemolysin HpmA to be the key effector for host cell destruction. Spatially separated coinfections demonstrated that synergism between Candida and Proteus is induced by contact, but also by soluble factors. Specifically, we identified Candida-mediated glucose consumption and farnesol production as potential triggers for Proteus virulence. In summary, our study demonstrates that coinfection of enterocytes with C. albicans and P. mirabilis can result in increased host cell damage which is mediated by bacterial virulence factors as a result of fungal niche modification via nutrient consumption and production of soluble factors. This supports the notion that certain fungal-bacterial combinations have the potential to result in enhanced virulence in niches such as the gut and might therefore promote translocation and dissemination.

Place, publisher, year, edition, pages
Frontiers Media S.A., 2022. Vol. 12, article id 866416
Keywords [en]
Candida albicans, coinfection, cross-kingdom interaction, enterocytes, Proteus mirabilis, synergism
National Category
Microbiology Microbiology in the medical area
Identifiers
URN: urn:nbn:se:umu:diva-203157DOI: 10.3389/fcimb.2022.866416ISI: 000803617400001PubMedID: 35651758Scopus ID: 2-s2.0-85131270555OAI: oai:DiVA.org:umu-203157DiVA, id: diva2:1727435
Available from: 2023-01-16 Created: 2023-01-16 Last updated: 2023-01-16Bibliographically approved

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Monsen, Tor J.

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