Deletion of Gliotoxin Biosynthesis Remodels the Intra- and Extracellular Metabolic Status of Aspergillus fumigatus, Alters Its Virulence-Related Phenotypes, and Modulates Host Immune Responses_culture supernatant

ABSTRACT:

Gliotoxin is a secondary metabolite produced by Aspergillus fumigatus, known to play a significant role in immune regulation and virulence phenotypes. This study investigates how the deletion of gliotoxin biosynthesis remodels the metabolic state of A. fumigatus and subsequently affects host immune responses. We employed a multi-omics approach, integrating fungal metabolomics and host transcriptomics data, to assess the impact of gliotoxin deletion on intra- and extracellular metabolic processes. The results showed that the loss of gliotoxin biosynthesis significantly altered the metabolic profile of A. fumigatus, with distinct changes observed in metabolites from both fungal mycelia and culture supernatants. These metabolic alterations were closely linked to changes in host cellular immune-related pathways. Notably, in macrophages and epithelial cells, treatment with gliotoxin led to significant changes in immune gene expression, revealing its role in modulating host immune responses.

Furthermore, treating macrophages with gliotoxin inhibited the secretion of inflammatory cytokines and reduced the cells' phagocytic capacity for A. fumigatus conidia, indicating that gliotoxin may play a role in suppressing host defense mechanisms. However, transcriptomic analysis also suggested that exposure to gliotoxin could promote the expression of certain immune genes, pointing to a complex interaction between the fungal metabolite and the host immune system. Through integrative analysis, we identified key metabolic and immune pathways affected by gliotoxin. These findings provide new insights into the impact of gliotoxin deletion on fungal virulence and host immunity, and offer a theoretical basis for potential therapeutic strategies in managing Aspergillus fumigatus infections.

INSTRUMENT(S): Liquid Chromatography MS - negative - reverse-phase, Liquid Chromatography MS - positive - reverse-phase

PROVIDER: MTBLS14011 | MetaboLights | 2026-05-11

REPOSITORIES: MetaboLights