A Fungal Sterylglucosidase at the Intersection of Virulence, Host Immunity, and Therapeutic Development

Human fungal infections (mycoses) cause significant morbidity and mortality in high-risk populations. Contemporary antifungal therapies rely heavily on three classes of antifungal drugs, and to date, no fungal vaccine is in clinical use for invasive mycosis. A major gap in knowledge related to fungal vaccine development is identifying lasting mechanisms of protective immunity in immunocompromised individuals. Recent studies in Cryptococcus neoformans and now Aspergillus fumigatus have identified a fungal sterylglucosidase essential for pathogenesis and virulence in murine models of mycoses. Fungal strains deficient in this sterylglucosidase can surprisingly also induce substantial immune-mediated protection against subsequent challenge with wild-type strains in multiple immunocompromised murine models of mycoses. Here, I discuss the implications and future directions of these exciting and impactful results.