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A novel pan-fungal screening platform for antifungal drug discovery: proof of principle study

Summary

Researchers developed a faster, more efficient screening method to test potential antifungal drugs against multiple disease-causing fungi simultaneously. Using an improved growth medium and screening 500 chemical fragments, they identified compounds with antifungal activity and demonstrated the platform can reliably detect promising drug candidates. This approach could accelerate the discovery of new antifungal medications, which are urgently needed as fungi develop resistance to current treatments.

Background

Current antifungal drugs face limitations including toxicity, drug interactions, and resistance. Fungal pathogen screening traditionally focuses on single species before assessing broader activity. A standardized pan-fungal screening approach could improve efficiency in early-stage antifungal drug discovery.

Objective

To develop a standardized phenotypic assay for screening against multiple WHO-defined critical and high-priority fungal pathogens using an enriched media formulation to support pan-fungal growth in high-throughput conditions.

Results

Growth was significantly improved in 7 of 12 species in fRPMI. All five assays achieved high-quality z-factors (≥0.5). Twenty-three compounds demonstrated antifungal activity against at least one species, of which five were identified as having pan-assay interference or broad toxicity. Multiple compounds showed multi-species activity.

Conclusion

A reproducible pan-fungal phenotypic screening platform was successfully established using optimized conditions and fRPMI medium. This approach enhances efficiency of early-stage antifungal drug discovery and can accommodate additional fungal species and screening modalities.
  • Published in:Antimicrobial Agents and Chemotherapy,
  • Study Type:Proof of Principle Study,
  • Source: 10.1128/aac.01328-24, PMID: 40167378
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