Department of Microbiome Dynamics, Leibniz Institute for Natural Product Research and Infection Biology (Leibniz-HKI), 07745, Jena, Germany.
Department of Molecular and Applied Microbiology, Leibniz Institute for Natural Product Research and Infection Biology (Leibniz-HKI), 07745, Jena, Germany.
Nat Commun. 2023 Jul 20;14(1):4369. doi: 10.1038/s41467-023-39982-5.
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.
烟曲霉是一种机会性人类病原体，常感染囊性纤维化患者的肺部，是免疫功能低下患者感染性疾病死亡的最常见原因之一。在这里，我们构建了 252 株特定的、全基因组规模的烟曲霉代谢模型，以研究和更好地理解其致病多功能性的代谢成分。这些模型表明，23.1%的烟曲霉代谢反应在菌株间没有保守性，主要与氨基酸、核苷酸和氮代谢有关。非保守反应和支持生长的反应通量的特征足以区分菌株，例如通过环境或临床来源。此外，对 40 名囊性纤维化患者（15 名女性，25 名男性）在诊断为烟曲霉定植前后的痰液进行的鸟枪法宏基因组学分析表明，真菌将肺部微生物组塑造成更有利于真菌生长的环境，与芳香族氨基酸的可用性和莽草酸途径有关。我们的发现为开发药物或微生物组干预策略提供了起点，这些策略针对真菌在人类肺部这种非天然环境中的生存和定植的代谢需求。
