Department of Microbial Pathogenicity Mechanisms, Leibniz Institute for Natural Product Research and Infection Biology - Hans-Knoell-Institute, Jena, Germany.
Systems Biology and Bioinformatics Unit, Leibniz Institute for Natural Product Research and Infection Biology - Hans-Knoell-Institute, Jena, Germany.
Nat Commun. 2022 Jun 9;13(1):3192. doi: 10.1038/s41467-022-30661-5.
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.
肠道微生物群落失调会引发共生念珠菌物种的过度生长 - 这是播散性念珠菌病的主要诱发因素。共生细菌，如鼠李糖乳杆菌，可以拮抗白色念珠菌的致病性。在这里，我们通过整合转录组学和代谢组学以及反向遗传学来研究白色念珠菌、鼠李糖乳杆菌和肠道上皮细胞之间的相互作用。非靶向代谢组学和计算机模拟表明，肠道上皮细胞在代谢上促进细菌生长，导致细菌产生抗真菌毒性化合物。此外，细菌的生长改变了代谢环境，包括去除白色念珠菌偏好的营养源。这伴随着白色念珠菌的转录组和代谢变化，包括与毒力相关基因的表达改变。我们的结果表明，细菌的肠道定植可以通过重塑代谢环境来拮抗白色念珠菌，迫使代谢适应，从而降低真菌的致病性。
