Post-Translational Modifications Drive Success and Failure of Fungal–Host Interactions

Post-translational modifications (PTMs) change the structure and function of proteins and regulate a diverse array of biological processes. Fungal pathogens rely on PTMs to modulate protein production and activity during infection, manipulate the host response, and ultimately, promote fungal survival. Given the high mortality rates of fungal infections on a global scale, along with the emergence of antifungal-resistant species, identifying new treatment options is critical. In this review, we focus on the role of PTMs (e.g., phosphorylation, acetylation, ubiquitination, glycosylation, and methylation) among the highly prevalent and medically relevant fungal pathogens, Candida spp., Aspergillus spp., and Cryptococcus spp. We explore the role of PTMs in fungal stress response and host adaptation, the use of PTMs to manipulate host cells and the immune system upon fungal invasion, and the importance of PTMs in conferring antifungal resistance. We also provide a critical view on the current knowledgebase, pose questions key to our understanding of the intricate roles of PTMs within fungal pathogens, and provide research opportunities to uncover new therapeutic strategies.