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

Alonso-Roman R, Last A, Mirhakkak MH, Sprague JL, Möller L, Großmann P, Graf K, Gratz R, Mogavero S, Vylkova S, Panagiotou G, Schäuble S, Hube B, Gresnigt MS (2022) Lactobacillus rhamnosus colonisation antagonizes Candida albicans by forcing metabolic adaptations that compromise pathogenicity. Nat Commun 13(1), 3192.

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.

Leibniz-HKI-Authors

Raquel Alonso-Román
Katja Graf
Rena Rebecca Gratz
Mark Gresnigt
Peter Großmann
Bernhard Hube
Antonia Last
Mohammadhassan Mirhakkak Esfahani
Selene Mogavero
Lars Möller
Gianni Panagiotou
Sascha Schäuble
Jakob Sprague
Slavena Vylkova

Awards

DGHM-Paper of the Month August 2022

Identifier

doi: 10.1038/s41467-022-30661-5

PMID: 35680868