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Label-Free Quantitative Proteomics Workflow for Discovery-Driven Host-Pathogen Interactions
Published on: October 20, 2020
Breaking down biofilms across critical priority fungal pathogens: proteomics and computational innovation for
Oscar Romero1, Jennifer Geddes-McAlister1
1Department of Molecular and Cellular Biology, University of Guelph, Guelph, Ontario, Canada.
Abstract:
Fungal biofilms are complex microbial structures associated with persistent and progressive infections, such as cryptococcal meningitis, invasive aspergillosis, and invasive candidiasis, leading to thousands of deaths annually. The prevalence of fungal biofilm formation during infections, with its heightened resistance to antifungal drugs, highlights the urgency for the discovery and development of new antifungals with antibiofilm activity. Current advances in mass spectrometry-based proteomics and computational platforms provide a powerful toolkit to accelerate drug discovery from target identification to optimization of a lead molecule. In this review, we highlight fungal biofilms of four critical priority fungal pathogens (as deemed by the World Health Organization) and define important technological considerations for proteomics and computational methodologies. Additionally, we explore recent proteomics and computational applications within fungal biofilms for the identification and elucidation of biological mechanisms underscoring biofilm formation as well as the discovery of novel putative antibiofilm targets.
Insights
Fungal biofilms cause deadly infections and resist drugs. New proteomics and computational tools accelerate the discovery of novel antifungal drugs targeting these biofilms.
Area of Science:
- Microbiology
- Mycology
- Infectious Diseases
Background:
- Fungal biofilms are resilient microbial communities responsible for persistent, life-threatening infections like cryptococcal meningitis, invasive aspergillosis, and candidiasis.
- The high resistance of fungal biofilms to antifungal agents necessitates the urgent development of novel therapeutics with antibiofilm capabilities.
Purpose of the Study:
- This review highlights fungal biofilms of WHO priority pathogens.
- It defines technological considerations for proteomics and computational methods in antifungal drug discovery.
- The review explores applications of these methods for identifying antibiofilm targets and understanding biofilm formation.
Main Methods:
- Mass spectrometry-based proteomics enables large-scale protein analysis.
- Computational platforms facilitate data analysis and target identification.
- The review synthesizes current research on proteomics and computational approaches in fungal biofilms.
Main Results:
- Proteomics and computational tools accelerate antifungal drug discovery from target identification to lead optimization.
- These methodologies aid in elucidating biological mechanisms of biofilm formation.
- Novel putative antibiofilm targets have been identified.
Conclusions:
- Advanced proteomics and computational strategies are crucial for combating fungal biofilm infections.
- These integrated approaches offer a powerful toolkit for discovering new antifungals with antibiofilm activity.
- Addressing WHO priority fungal pathogens requires innovative therapeutic strategies targeting biofilms.
