Insights from Mass Spectrometry-Based Proteomics on <em>Cryptococcus neoformans</em>

Cryptococcus neoformans is an opportunistic fungal pathogen and causative agent of cryptococcosis and cryptococcal meningitis (CM). Cryptococcal disease accounts for up to 19% of AIDS-related mortalities globally, warranting its label as a pathogen of critical priority by the World Health Organization. Standard treatments for CM rely heavily on high doses of antifungal agents for long periods of time, contributing to the growing issue of antifungal resistance. Moreover, mortality rates for CM are still incredibly high (13-78%). Attempts to create new and effective treatments have been slow due to the complex and diverse set of immune evasive and survival-enhancing virulence factors that C. neoformans employs. To bolster the development of better clinical tools, deeper study into host-Cryptococcus proteomes is needed to identify clinically relevant proteins, pathways, antigens, and beneficial host response mechanisms. Mass spectrometry-based proteomics are invaluable tools for investigating these complex questions. Here, we discuss some of the insights into cryptococcal disease and biology learned using proteomics, including target proteins and pathways regulating Cryptococcus virulence factors, metabolism, and host defense responses. By utilizing proteomics to probe deeper into these protein interaction networks, new clinical tools for detecting, diagnosing, and treating C. neoformans can be developed.