Exploring the concordance of Aspergillus fumigatus pathogenicity in mice and Toll-deficient flies

Area of Science:

• Medical Mycology
• Infectious Diseases
• Model Organisms

Background:

• Aspergillus fumigatus is an opportunistic fungal pathogen causing invasive aspergillosis.
• Murine models are standard for studying A. fumigatus pathogenicity.
• Alternative models are needed to complement murine studies.

Purpose of the Study:

• To assess the pathogenicity of characterized Aspergillus fumigatus mutants in a Toll-deficient Drosophila melanogaster fly model.
• To evaluate the concordance between murine and fly models of invasive aspergillosis.

Main Methods:

• Six previously characterized A. fumigatus mutants with known virulence in mice were used.
• Pathogenicity was assessed in Toll-deficient Drosophila melanogaster flies.
• Virulence was compared between the fly model and previous murine data.

Main Results:

• Four out of six A. fumigatus mutants exhibited attenuated virulence in the fly model, mirroring their reduced virulence in mice.
• Mutants with defects in siderophore biosynthesis (DeltasidA, DeltasidD), PABA metabolism (H515), and starvation stress response (DeltacpcA) showed attenuated virulence in flies.
• The DeltasidG mutant, defective in extracellular siderophore biosynthesis, retained full virulence in flies, consistent with mouse model findings.

Conclusions:

• Toll-deficient Drosophila melanogaster serves as a viable model for assessing A. fumigatus pathogenicity.
• There is a high degree of concordance in pathogenicity between fly and murine models of invasive aspergillosis.
• The fly model can effectively predict virulence phenotypes observed in mammalian systems.