Genome-scale metabolic modeling of Aspergillus fumigatus strains reveals growth dependencies on the lung microbiome
Abstract 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 i...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2023-07-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-023-39982-5 |
| _version_ | 1797774120474116096 |
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| author | Mohammad H. Mirhakkak Xiuqiang Chen Yueqiong Ni Thorsten Heinekamp Tongta Sae-Ong Lin-Lin Xu Oliver Kurzai Amelia E. Barber Axel A. Brakhage Sebastien Boutin Sascha Schäuble Gianni Panagiotou |
| author_facet | Mohammad H. Mirhakkak Xiuqiang Chen Yueqiong Ni Thorsten Heinekamp Tongta Sae-Ong Lin-Lin Xu Oliver Kurzai Amelia E. Barber Axel A. Brakhage Sebastien Boutin Sascha Schäuble Gianni Panagiotou |
| author_sort | Mohammad H. Mirhakkak |
| collection | DOAJ |
| description | Abstract 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. |
| first_indexed | 2024-03-12T22:16:23Z |
| format | Article |
| id | doaj.art-e8d5fb99e5474f61bb345e85e225884e |
| institution | Directory Open Access Journal |
| issn | 2041-1723 |
| language | English |
| last_indexed | 2024-03-12T22:16:23Z |
| publishDate | 2023-07-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj.art-e8d5fb99e5474f61bb345e85e225884e2023-07-23T11:19:38ZengNature PortfolioNature Communications2041-17232023-07-0114111710.1038/s41467-023-39982-5Genome-scale metabolic modeling of Aspergillus fumigatus strains reveals growth dependencies on the lung microbiomeMohammad H. Mirhakkak0Xiuqiang Chen1Yueqiong Ni2Thorsten Heinekamp3Tongta Sae-Ong4Lin-Lin Xu5Oliver Kurzai6Amelia E. Barber7Axel A. Brakhage8Sebastien Boutin9Sascha Schäuble10Gianni Panagiotou11Department of Microbiome Dynamics, Leibniz Institute for Natural Product Research and Infection Biology (Leibniz-HKI)Department of Microbiome Dynamics, Leibniz Institute for Natural Product Research and Infection Biology (Leibniz-HKI)Department of Microbiome Dynamics, Leibniz Institute for Natural Product Research and Infection Biology (Leibniz-HKI)Department of Molecular and Applied Microbiology, Leibniz Institute for Natural Product Research and Infection Biology (Leibniz-HKI)Department of Microbiome Dynamics, Leibniz Institute for Natural Product Research and Infection Biology (Leibniz-HKI)Department of Microbiome Dynamics, Leibniz Institute for Natural Product Research and Infection Biology (Leibniz-HKI)Institute for Hygiene and Microbiology, University of WürzburgJunior Research Group Fungal Informatics, Institute of Microbiology, Friedrich-Schiller-University JenaDepartment of Molecular and Applied Microbiology, Leibniz Institute for Natural Product Research and Infection Biology (Leibniz-HKI)Department of Infectious Diseases and Microbiology, University of LübeckDepartment of Microbiome Dynamics, Leibniz Institute for Natural Product Research and Infection Biology (Leibniz-HKI)Department of Microbiome Dynamics, Leibniz Institute for Natural Product Research and Infection Biology (Leibniz-HKI)Abstract 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.https://doi.org/10.1038/s41467-023-39982-5 |
| spellingShingle | Mohammad H. Mirhakkak Xiuqiang Chen Yueqiong Ni Thorsten Heinekamp Tongta Sae-Ong Lin-Lin Xu Oliver Kurzai Amelia E. Barber Axel A. Brakhage Sebastien Boutin Sascha Schäuble Gianni Panagiotou Genome-scale metabolic modeling of Aspergillus fumigatus strains reveals growth dependencies on the lung microbiome Nature Communications |
| title | Genome-scale metabolic modeling of Aspergillus fumigatus strains reveals growth dependencies on the lung microbiome |
| title_full | Genome-scale metabolic modeling of Aspergillus fumigatus strains reveals growth dependencies on the lung microbiome |
| title_fullStr | Genome-scale metabolic modeling of Aspergillus fumigatus strains reveals growth dependencies on the lung microbiome |
| title_full_unstemmed | Genome-scale metabolic modeling of Aspergillus fumigatus strains reveals growth dependencies on the lung microbiome |
| title_short | Genome-scale metabolic modeling of Aspergillus fumigatus strains reveals growth dependencies on the lung microbiome |
| title_sort | genome scale metabolic modeling of aspergillus fumigatus strains reveals growth dependencies on the lung microbiome |
| url | https://doi.org/10.1038/s41467-023-39982-5 |
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