Revealing the dynamics of fungal disease with proteomics

The occurrence and distribution of new and re-emerging fungal pathogens, along with rates of antifungal resistance, are rising across the globe, and correspondingly, so are our awareness and call for action to address this public health concern. To effectively detect, monitor, and treat fungal infections, biological insights into the mechanisms that regulate pathogenesis, influence survival, and promote resistance are urgently needed. Mass spectrometry-based proteomics is a high-resolution technique that enables the identification and quantification of proteins across diverse biological systems to better understand the biology driving phenotypes. In this review, we highlight dynamic and innovative applications of proteomics to characterize three critical fungal pathogens (i.e., Candida spp., Cryptococcus spp., and Aspergillus spp.) causing disease in humans. We present strategies to investigate the host–pathogen interface, virulence factor production, and protein-level drivers of antifungal resistance. Through these studies, new opportunities for biomarker development, drug target discovery, and immune system remodeling are discussed, supporting the use of proteomics to combat a plethora of fungal diseases threatening global health.