Resolving the Temporal Splenic Proteome during Fungal Infection for Discovery of Putative Dual Perspective Biomarker Signatures

Fungalpathogens are emerging threats to global health with therise of incidence associated with climate change and increased geographicaldistribution; factors also influencing host susceptibility to infection.Accurate detection and diagnosis of fungal infections is paramountto offer rapid and effective therapeutic options. For improved diagnostics,the discovery and development of protein biomarkers presents a promisingavenue; however, this approach requires a priori knowledgeof infection hallmarks. To uncover putative novel biomarkers of disease,profiling of the host immune response and pathogen virulence factorproduction is indispensable. In this study, we use mass-spectrometry-basedproteomics to resolve the temporal proteome of Cryptococcusneoformans infection of the spleen following a murine modelof infection. Dual perspective proteome profiling defines global remodelingof the host over a time course of infection, confirming activationof immune associated proteins in response to fungal invasion. Conversely,pathogen proteomes detect well-characterized C. neoformans virulence determinants, along with novel mapped patterns of pathogenesisduring the progression of disease. Together, our innovative systematicapproach confirms immune protection against fungal pathogens and exploresthe discovery of putative biomarker signatures from complementarybiological systems to monitor the presence and progression of cryptococcaldisease.