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Discovery of novel targets for important human and plant fungal pathogens via an automated computational pipeline HitList

Summary

Scientists developed a computer program called HitList that searches through fungal genes to find new targets for antifungal medicines. The program identifies proteins that are unique to harmful fungi and missing from humans and plants, making them ideal drug targets. The study found several promising new protein targets that could lead to development of more effective antifungal drugs to treat both human fungal infections and crop diseases caused by fungi.

Background

Fungal pathogens cause significant mortality in humans and major crop losses globally, with emerging drug resistance limiting the effectiveness of current antifungal treatments. The limited number of antifungal modes of action and shared eukaryotic ancestry between fungi and hosts creates challenges in developing new therapeutics without host toxicity.

Objective

Develop an automated bioinformatics pipeline called HitList to identify novel fungal-specific protein targets essential for pathogen viability that are absent in human and plant hosts for WHO-designated fungal pathogens and top agricultural fungal pathogens.

Results

HitList validated known antifungal targets (Fas1, Fas2, Alr1, Chs2) and identified eight novel potential targets: Erg8, Fcy21, Ilv3, Ilv5, Rib3, Rib5, Ssy1, and Ste12. Some targets showed suitability for WHO pathogens while others were better suited for agricultural pathogens, with potential for broad-spectrum development.

Conclusion

The HitList pipeline successfully identified both previously known and novel fungal-specific protein targets that could serve as foundations for developing new antifungal compounds with novel modes of action to combat drug-resistant fungi in both clinical and agricultural settings.
  • Published in:PLoS One,
  • Study Type:Computational Study,
  • Source: PMID: 40460077, DOI: 10.1371/journal.pone.0323991
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