11-12 November 2021
Digital (Zoom)
Europe/Berlin timezone

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

12 Nov 2021, 16:20
30m
Digital (Zoom)

Digital (Zoom)

Speakers

Ms Raquel Alonso-Román (Department of Microbial Pathogenicity Mechanisms – Hans Knöll Institute, Jena, Germany) Dr Sascha Schäuble (Systems Biology and Bioinformatics Unit – Hans Knöll Institute, Jena, Germany)

Description

Dysbiosis of the intestinal bacterial microbiota caused by antibiotic treatment can initiate overgrowth of commensal Candida species – a predisposing factor for disseminated candidiasis. The gut colonizing bacterium and probiotic Lactobacillus rhamnosus can antagonize C. albicans, the most frequent cause of disseminated candidiasis. To uncover the molecular mechanisms of bacterial antagonism, we investigated the interplay between
C. albicans, L. rhamnosus, and intestinal epithelial cells (IECs) by integrating transcriptional and metabolic profiling, and reverse genetics. Untargeted metabolomics combined with in silico modelling of L. rhamnosus metabolism not only identified antivirulence and antifungal metabolites, but also suggested that IECs foster bacterial growth by releasing specific metabolites such as citric acid, gamma-glutamylalanine and carnitine, which was confirmed experimentally. Bacterial growth on IECs modifies the metabolic environment, including the removal of carbon sources energetically favoured by C. albicans. Consequently, C. albicans is forced to transcriptionally rewire its metabolism and cell biology, which is associated with the reprogramming of specific genes that play a role in virulence. Deletion mutants of these genes exhibit a reduced damage potential, providing a causal explanation for the antagonistic effects driven by metabolic alterations in our model. Altogether, our research suggests that intestinal colonization with bacteria can antagonize C. albicans by reshaping the metabolic environment, forcing metabolic adaptations and consequently reducing fungal pathogenicity.

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