2 items tagged with 'GSMM'.
Abstract (Expand)
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.
Authors: R. Alonso-Roman, A. Last, M. H. Mirhakkak, J. L. Sprague, L. Moller, P. Grossmann, K. Graf, R. Gratz, S. Mogavero, S. Vylkova, G. Panagiotou, S. Schauble, B. Hube, M. S. Gresnigt
Date Published: 9th Jun 2022
Publication Type: Journal
PubMed ID: 35680868
Citation: Nat Commun. 2022 Jun 9;13(1):3192. doi: 10.1038/s41467-022-30661-5.
Created: 19th Jan 2024 at 12:21
Abstract (Expand)
Aspergillus fumigatus, an opportunistic human pathogen, frequently infects the lungs of people with cystic fibrosis and is one of the most common causes of infectious-disease death in immunocompromised … patients. Here, we construct 252 strain-specific, genome-scale metabolic models of this important fungal pathogen to study and better understand the metabolic component of its pathogenic versatility. The models show that 23.1% of A. fumigatus metabolic reactions are not conserved across strains and are mainly associated with amino acid, nucleotide, and nitrogen metabolism. Profiles of non-conserved reactions and growth-supporting reaction fluxes are sufficient to differentiate strains, for example by environmental or clinical origin. In addition, shotgun metagenomics analysis of sputum from 40 cystic fibrosis patients (15 females, 25 males) before and after diagnosis with an A. fumigatus colonization suggests that the fungus shapes the lung microbiome towards a more beneficial fungal growth environment associated with aromatic amino acid availability and the shikimate pathway. Our findings are starting points for the development of drugs or microbiome intervention strategies targeting fungal metabolic needs for survival and colonization in the non-native environment of the human lung.
Authors: M. H. Mirhakkak, X. Chen, Y. Ni, T. Heinekamp, T. Sae-Ong, L. L. Xu, O. Kurzai, A. E. Barber, A. A. Brakhage, S. Boutin, S. Schauble, G. Panagiotou
Date Published: 20th Jul 2023
Publication Type: Journal
PubMed ID: 37474497
Citation: Nat Commun. 2023 Jul 20;14(1):4369. doi: 10.1038/s41467-023-39982-5.
Created: 19th Jan 2024 at 12:08