Host-Pathogen Interaction Activated Biosynthesis of Natural Products.
Yukiko Ujie1, Shun Saito1, Chisato Iwata1
1Faculty of Science and Technology, Keio University, Yokohama 223-8522, Japan.
Journal of Natural Products
|August 28, 2025
Summary
Pathogenic fungi and immune cells interact, triggering the production of new survival compounds. This study reveals how host-pathogen interactions activate fungal genes, producing novel metabolites like fumigatinolactone.
Area of Science:
- Microbiology
- Immunology
- Natural Product Chemistry
Background:
- Pathogenic microorganisms may produce survival compounds when attacked by immune cells.
- Understanding host-pathogen interactions is crucial for developing new antimicrobial strategies.
Purpose of the Study:
- To investigate the interaction between pathogenic fungi and immune cells.
- To isolate and characterize novel natural products produced during this interaction.
- To elucidate the mechanisms underlying the production of these compounds.
Main Methods:
- Coculture of *Aspergillus fumigatus* with RAW264 mouse macrophage-like cells.
- Isolation and structural elucidation of fumigatinolactone (1).
- Investigation of the biosynthetic pathway and regulatory mechanisms.
Main Results:
- Fumigatinolactone (1) was isolated as a new natural product.
- Compound 1 is formed via nonenzymatic coupling of fumigatin (4) and fumarylazlactone (5).
- Fungal response to nitric oxide (NO) induced fumigatin (4) production, while iron starvation induced fumarylazlactone (5) production.
- Compounds 1-4 inhibited NO production by macrophages, suggesting a fungal defense mechanism.
Conclusions:
- Host-pathogen survival interactions can activate silent fungal genes to produce novel secondary metabolites.
- This study provides the first elucidation of interaction mechanisms between pathogen and immune cells leading to new compound production.
- Findings suggest that manipulating host-pathogen interactions could be a strategy to discover new fungal metabolites.
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