Mass Spectrometry-Based Proteomics of Fungal Pathogenesis, Host–Fungal Interactions, and Antifungal Development

Abstract

The prevalence of fungal diseases is increasing on a global scale, ranging from acute to systemic infections caused by commensal or pathogenic microorganisms, often associated with the immune status of the host. Morbidity and mortality rates remain high and our ability to treat fungal infections is challenged by a limited arsenal of antifungal agents and the emergence of drug resistant pathogens. There is a high demand for new approaches to elucidate the fungal mechanisms of pathogenesis and the interplay between host and pathogen to discover novel treatment options. Moreover, the need for improved drug efficacy and reduced host toxicity requires the identification and characterization of antifungal biological targets and molecular mechanisms of action. Mass spectrometry (MS)-based proteomics is a rapidly advancing field capable of addressing these priorities by providing comprehensive information on the dynamics of cellular processes, modifications, and interactions. In this Review, we focus on applications of MS-based proteomics in a diverse array of fungal pathogens and host systems to define and distinguish the molecular details of fungal pathogenesis and host–fungal interactions. We also explore the emerging role of MS-based proteomics in the discovery and development of novel antifungal therapies and provide insight into the future of MS-based proteomics in fungal biology.

Immunoproteomics Reveals Pathogen’s Antigens Involved in Homo sapiens–Histoplasma capsulatum Interaction and Specific Linear B-Cell Epitopes in Histoplasmosis

“…The use of proteomic tools for the identification of proteins involved in the parasite-host interaction, and presumed to be antigenic targets, has been applied to pathogenic fungi studies ( Crockett et al., 2012 ; Ball et al., 2019 ; Moreira et al., 2020 ). Thus, our work used co-immunoprecipitation followed by mass spectrometry to identify proteins involved the interplay between host and pathogen, specifically those recognized by B-cell receptor and their B-cell antibodies products, as with the identification of presumed antigenic targets with possible application in diagnostic tests.…”

Fun(gi)omics: Advanced and Diverse Technologies to Explore Emerging Fungal Pathogens and Define Mechanisms of Antifungal Resistance

“…Mycology-focused research has profoundly progressed over the last 2 decades due to the impressive technological advancement of mass spectrometry (MS)-based proteomics (73). Proteomics profiles the broad view of gene expression patterns, including quantification of protein production, posttranslational modifications (PTMs), alternate protein isoforms, and interaction networks (74).…”

Quantitative Proteomic Profiling of Murine Ocular Tissue and the Extracellular Environment

“…The information obtained from quantitative proteomic profiling can inform treatment strategies, patient stratification, molecular mechanisms underpinning phenotypic observations and details pertaining to signaling networks, and protein-protein interactions critical to the evaluated criteria (Mann, Kulak, Nagaraj, & Cox, 2013). In addition, proteomic profiling can provide valuable insight into the interplay between host and pathogen during infection and generate large datasets outlining changes from these dual perspectives in a single experiment (Ball, Bermas, Carruthers-Lay, & Geddes-McAlister, 2019;Jean Beltran, Federspiel, Sheng, & Cristea, 2017;Sukumaran et al, 2019). For example, proteomic profiling of the ocular surface during infection with Pseudomonas aeruginosa, a Gramnegative bacterial pathogen and the primary causative agent of ocular keratitis, defines global and site-specific host responses to infection and uncovers potential biomarkers for prognostic and diagnostic purposes (Yeung, Gadjeva, & Geddes-McAlister, 2020).…”