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

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.

Abstract

Commensal bacteria such as Lactobacillus rhamnosus can inhibit the pathogenicity of the fungus Candida albicans. Here, Alonso-Roman et al. investigate the interplay between C. albicans, L. rhamnosus and intestinal epithelial cells, showing that changes in the metabolic environment, induced by the bacteria, trigger adaptations in C. albicans that reduce fungal pathogenicity.