Lactobacillus rhamnosus colonisation antagonizes Candida albicans by forcing metabolic adaptations that compromise pathogenicity

Raquel Alonso-Roman, Antonia Last, Mohammad H. Mirhakkak, Jakob L. Sprague, Lars Möller, Peter Großmann, Katja Graf, Rena Gratz, Selene Mogavero, Slavena Vylkova, Gianni Panagiotou, Sascha Schäuble, Bernhard Hube () and Mark S. Gresnigt
Additional contact information
Raquel Alonso-Roman: Leibniz Institute for Natural Product Research and Infection Biology - Hans-Knoell-Institute
Antonia Last: Leibniz Institute for Natural Product Research and Infection Biology - Hans-Knoell-Institute
Mohammad H. Mirhakkak: Leibniz Institute for Natural Product Research and Infection Biology - Hans-Knoell-Institute
Jakob L. Sprague: Leibniz Institute for Natural Product Research and Infection Biology - Hans-Knoell-Institute
Lars Möller: Leibniz Institute for Natural Product Research and Infection Biology - Hans-Knoell-Institute
Peter Großmann: Leibniz Institute for Natural Product Research and Infection Biology - Hans-Knoell-Institute
Katja Graf: Leibniz Institute for Natural Product Research and Infection Biology - Hans-Knoell-Institute
Rena Gratz: Leibniz Institute for Natural Product Research and Infection Biology - Hans-Knoell-Institute
Selene Mogavero: Leibniz Institute for Natural Product Research and Infection Biology - Hans-Knoell-Institute
Slavena Vylkova: Leibniz Institute for Natural Product Research and Infection Biology – Hans-Knoell-Institute
Gianni Panagiotou: Leibniz Institute for Natural Product Research and Infection Biology - Hans-Knoell-Institute
Sascha Schäuble: Leibniz Institute for Natural Product Research and Infection Biology - Hans-Knoell-Institute
Bernhard Hube: Leibniz Institute for Natural Product Research and Infection Biology - Hans-Knoell-Institute
Mark S. Gresnigt: Leibniz Institute for Natural Product Research and Infection Biology - Hans-Knoell-Institute

Nature Communications, 2022, vol. 13, issue 1, 1-15

Abstract: Abstract Intestinal microbiota dysbiosis can initiate overgrowth of commensal Candida species – a major predisposing factor for disseminated candidiasis. Commensal bacteria such as Lactobacillus rhamnosus can antagonize Candida albicans pathogenicity. Here, we investigate the interplay between C. albicans, L. rhamnosus, and intestinal epithelial cells by integrating transcriptional and metabolic profiling, and reverse genetics. Untargeted metabolomics and in silico modelling indicate that intestinal epithelial cells foster bacterial growth metabolically, leading to bacterial production of antivirulence compounds. In addition, bacterial growth modifies the metabolic environment, including removal of C. albicans’ favoured nutrient sources. This is accompanied by transcriptional and metabolic changes in C. albicans, including altered expression of virulence-related genes. Our results indicate that intestinal colonization with bacteria can antagonize C. albicans by reshaping the metabolic environment, forcing metabolic adaptations that reduce fungal pathogenicity.

Date: 2022
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DOI: 10.1038/s41467-022-30661-5

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