Genome-scale metabolic modeling of Aspergillus fumigatus strains reveals growth dependencies on the lung microbiome.

Autor: Mirhakkak MH; Department of Microbiome Dynamics, Leibniz Institute for Natural Product Research and Infection Biology (Leibniz-HKI), 07745, Jena, Germany., Chen X; Department of Microbiome Dynamics, Leibniz Institute for Natural Product Research and Infection Biology (Leibniz-HKI), 07745, Jena, Germany., Ni Y; Department of Microbiome Dynamics, Leibniz Institute for Natural Product Research and Infection Biology (Leibniz-HKI), 07745, Jena, Germany., Heinekamp T; Department of Molecular and Applied Microbiology, Leibniz Institute for Natural Product Research and Infection Biology (Leibniz-HKI), 07745, Jena, Germany., Sae-Ong T; Department of Microbiome Dynamics, Leibniz Institute for Natural Product Research and Infection Biology (Leibniz-HKI), 07745, Jena, Germany., Xu LL; Department of Microbiome Dynamics, Leibniz Institute for Natural Product Research and Infection Biology (Leibniz-HKI), 07745, Jena, Germany., Kurzai O; Institute for Hygiene and Microbiology, University of Würzburg, 97080, Würzburg, Germany.; Research Group Fungal Septomics, Leibniz Institute of Natural Product Research and Infection Biology (Leibniz-HKI), 07745, Jena, Germany.; National Reference Center for Invasive Fungal Infections (NRZMyk), Leibniz Institute of Natural Product Research and Infection Biology (Leibniz-HKI), 07745, Jena, Germany., Barber AE; Junior Research Group Fungal Informatics, Institute of Microbiology, Friedrich-Schiller-University Jena, 07745, Jena, Germany., Brakhage AA; Department of Molecular and Applied Microbiology, Leibniz Institute for Natural Product Research and Infection Biology (Leibniz-HKI), 07745, Jena, Germany.; Institute of Microbiology, Friedrich Schiller University Jena, 07745, Jena, Germany., Boutin S; Department of Infectious Diseases and Microbiology, University of Lübeck, 23562, Lübeck, Germany.; Translational Lung Research Center Heidelberg (TLRC), German Center for Lung Research (DZL), University of Heidelberg, 69120, Heidelberg, Germany., Schäuble S; Department of Microbiome Dynamics, Leibniz Institute for Natural Product Research and Infection Biology (Leibniz-HKI), 07745, Jena, Germany. Sascha.Schaeuble@leibniz-hki.de., Panagiotou G; Department of Microbiome Dynamics, Leibniz Institute for Natural Product Research and Infection Biology (Leibniz-HKI), 07745, Jena, Germany. Gianni.Panagiotou@leibniz-hki.de.; Department of Medicine and State Key Laboratory of Pharmaceutical Biotechnology, University of Hong Kong, Hong Kong, China. Gianni.Panagiotou@leibniz-hki.de.; Friedrich Schiller University, Faculty of Biological Sciences, Jena, 07745, Germany. Gianni.Panagiotou@leibniz-hki.de.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2023 Jul 20; Vol. 14 (1), pp. 4369. Date of Electronic Publication: 2023 Jul 20.
DOI: 10.1038/s41467-023-39982-5
Abstrakt: 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.
(© 2023. The Author(s).)
Databáze: MEDLINE
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