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

Summary

Researchers created a computer program called HitList that searches fungal DNA to find new targets for antifungal medications. The program identified 16 promising protein targets that could be attacked by new antifungal drugs, including 8 completely new targets never before considered. This discovery could help develop new antifungal treatments to fight drug-resistant fungal infections in both humans and crops.

Background

Fungal pathogens cause significant human mortality and agricultural losses, with emerging drug resistance limiting current antifungal treatments. The limited number of antifungal modes of action and availability of pathogenic fungal genomes has created an opportunity for systematic target discovery.

Objective

Develop and validate an automated bioinformatics pipeline (HitList) to identify novel antifungal protein targets for WHO fungal priority pathogens and top 10 agricultural fungal pathogens through systematic comparative genomics.

Results

HitList identified 16 promising protein targets, including validation of known antifungal targets (Fas1, Fas2, Alr1, Fol1) and eight novel targets (Erg8, Fcy21, Ilv3, Ilv5, Rib3, Rib5, Ssy1, Ste12) not previously identified in the literature as antifungal targets.

Conclusion

HitList successfully identified both established and novel antifungal targets suitable for rational drug design. The pipeline is generalizable to any pathogen-host combination and could enable development of broad-spectrum antifungals with new modes of action to overcome existing drug resistance.
  • Published in:PLoS One,
  • Study Type:Bioinformatics Study,
  • Source: PMID: 40460077, DOI: 10.1371/journal.pone.0323991
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