Core N -Glycan Structures Are Critical for the Pathogenicity of Cryptococcus neoformans by Modulating Host Cell Death

Abstract

We previously reported that the outer mannose chains of N -glycans are dispensable for the virulence of C. neoformans , which is in stark contrast to findings for the other human-pathogenic yeast, Candida albicans . Here, we present evidence that an intact core N -glycan structure is required for C. neoformans pathogenicity by systematically analyzing alg3Δ, alg9Δ , and alg12Δ strains that have defects in lipid-linked N- glycan assembly and in in vivo virulence. The alg null mutants producing truncated core N -glycans were defective in inducing host cell death after phagocytosis, which is triggered as a mechanism of pulmonary escape and dissemination of C. neoformans , thus becoming inactive in causing fatal infection. The results clearly demonstrated the critical features of the N -glycan structure in mediating the interaction with host cells during fungal infection. The delineation of the roles of protein glycosylation in fungal pathogenesis not only provides insight into the glycan-based fungal infection mechanism but also will aid in the development of novel antifungal agents.