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A Dual-Readout High-Throughput Screening Assay for Small Molecules Active Against Aspergillus Fumigatus
Sarah R Beattie1, Damian J Krysan2,3,4
1Departments of Pediatrics, Carver College of Medicine, University of Iowa, Iowa City, IA, USA. sarah-r-beattie@uiowa.edu.
Abstract:
Human fungal infections caused by molds have been on the rise in recent years. These infections have high mortality rates compared to other fungal infections, and yet treatment options are limited due to resistance to clinical antifungals and lack of broad-spectrum activity against molds. Technical challenges associated with molds have limited large-throughput screening efforts for anti-mold compounds: therefore, we adapted an assay for use with A. fumigatus to help fill the gap in robust screening platforms for these organisms. This assay measures the release of the cytosolic enzyme adenylate kinase (AK) as a measure of fungal cell lysis and can also detect inhibition of germination as a reduction in the secretion of AK during vegetative growth. The ability to detect both lysis and inhibition of germination facilitates the identification of a wide range of compounds with different mechanisms of action, creating a strong screening platform for the identification of novel, anti-mold compounds.
Insights
Rising mold infections necessitate new treatments. A novel assay for Aspergillus fumigatus detects fungal cell lysis and germination inhibition, aiding the discovery of effective anti-mold compounds.
Area of Science:
- Medical Mycology
- Drug Discovery
- Biotechnology
Background:
- Human fungal infections caused by molds are increasing.
- Limited treatment options exist due to antifungal resistance and lack of broad-spectrum activity.
- Technical challenges hinder large-throughput screening for anti-mold compounds.
Purpose of the Study:
- To adapt a fungal cell lysis assay for use with Aspergillus fumigatus.
- To develop a robust screening platform for novel anti-mold compounds.
- To address the gap in high-throughput screening for mold-specific treatments.
Main Methods:
- Adapted an adenylate kinase (AK) release assay for Aspergillus fumigatus.
- Measured fungal cell lysis via AK release.
- Detected inhibition of germination by monitoring AK secretion during vegetative growth.
Main Results:
- Successfully adapted the AK release assay for A. fumigatus.
- The assay can detect both fungal cell lysis and inhibition of germination.
- This platform facilitates the identification of compounds with diverse mechanisms of action.
Conclusions:
- The developed assay provides a robust screening platform for anti-mold compounds.
- This platform can accelerate the discovery of novel treatments for invasive mold infections.
- Addressing technical challenges in mold screening is crucial for advancing antifungal therapies.
