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Cryptococcosis caused by  Cryptococcus neoformans  and  Cryptococcus gattii  affects a large population and is a cause of significant morbidity and mortality. Despite its public health burden, there are currently no vaccines against cryptococcosis and new strategies against such infections are needed. In this study, we demonstrate that  C. neoformans  has the biochemical ability to metabolize sterylglucosides (SGs), a class of immunomodulatory glycolipids. Genetic manipulations that eliminate cryptococccal sterylglucosidase lead to the accumulation of SGs and generate a mutant strain (Δ sgl1 ) that is non-pathogenic in the mouse models of cryptococcosis. Interestingly, this mutant strain acts as a vaccine strain and protects mice against cryptococcosis following infection with  C. neoformans  or  C. gattii . The immunity induced by the Δ sgl1  strain is not CD4 +  T-cells dependent. Immunocompromised mice, which lack CD4 +  T-cells, are able to control the infection by Δ sgl1  and acquire immunity against the challenge by wild-type  C. neoformans  following vaccination with the Δ sgl1  strain. These findings are particularly important in the context of HIV/AIDS immune deficiency and suggest that the Δ sgl1  strain might provide a potential vaccination strategy against cryptococcosis.

Role of Sterylglucosidase 1 (Sgl1) on the pathogenicity of Cryptococcus neoformans: potential applications for vaccine development