Breaking down biofilms across critical priority fungal pathogens: proteomics and computational innovation for mechanistic insights and new target discovery

Summary

Fungal infections like cryptococcal meningitis and invasive aspergillosis are becoming increasingly difficult to treat because fungi form protective structures called biofilms that resist our current medications. Researchers are using advanced techniques like mass spectrometry to identify the proteins that help fungi build these biofilms, combined with artificial intelligence tools to design new drugs that could break down these protective shields. This combined approach offers hope for developing better antifungal treatments that could save millions of lives.

Background

Fungal biofilms are complex microbial structures associated with persistent infections such as cryptococcal meningitis, invasive aspergillosis, and invasive candidiasis. These biofilms exhibit heightened resistance to antifungal drugs, contributing to thousands of deaths annually. The World Health Organization has designated four critical priority fungal pathogens: Cryptococcus neoformans, Aspergillus fumigatus, Candida albicans, and Candida auris.

Objective

This review highlights fungal biofilms of four critical priority fungal pathogens and defines important technological considerations for proteomics and computational methodologies. The authors explore recent proteomics and computational applications for identification and elucidation of biological mechanisms underlying biofilm formation and discovery of novel antibiofilm targets.

Results

Mass spectrometry-based proteomics identified key biofilm-associated proteins involved in metabolic shifts, oxidative stress response, adhesion, and morphological changes across the four pathogens. Heat shock protein 70 was elevated in biofilms of all three examined species. Computational approaches including AlphaFold predictions enabled virtual screening of potential ligands against identified biofilm targets.

Conclusion

Integration of mass spectrometry-based proteomics with computational tools like AlphaFold provides powerful approaches to identify novel antibiofilm targets and accelerate drug discovery. Future studies should combine proteomics discoveries with computational-based drug design, virtual HTS, and traditional HTS to develop new antifungals with enhanced antibiofilm activity against critical priority fungal pathogens.
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