title: Role of Sterylglucosidase 1 (Sgl1) on the pathogenicity of Cryptococcus neoformans: potential applications for vaccine development.
abstract: 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 (Δsgl1) 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 Δsgl1 strain is not CD4(+) T-cells dependent. Immunocompromised mice, which lack CD4(+) T-cells, are able to control the infection by Δsgl1 and acquire immunity against the challenge by wild-type C. neoformans following vaccination with the Δsgl1 strain. These findings are particularly important in the context of HIV/AIDS immune deficiency and suggest that the Δsgl1 strain might provide a potential vaccination strategy against cryptococcosis.
authors: Department of Molecular Genetics and Microbiology, Stony Brook University, Stony Brook NY, USA.
authors: Antonella
authors: A
authors: Rella
authors: Department of Molecular Genetics and Microbiology, Stony Brook University, Stony Brook NY, USA.
authors: Visesato
authors: V
authors: Mor
authors: Department of Molecular Genetics and Microbiology, Stony Brook University, Stony Brook NY, USA.
authors: Amir M
authors: AM
authors: Farnoud
authors: Department of Molecular Genetics and Microbiology, Stony Brook University, Stony Brook NY, USA.
authors: Ashutosh
authors: A
authors: Singh
authors: Department of Medicine, Stony Brook University, Stony Brook NY, USA.
authors: Achraf A
authors: AA
authors: Shamseddine
authors: Department of Molecular Genetics and Microbiology, Stony Brook University, Stony Brook NY, USA.
authors: Elitza
authors: E
authors: Ivanova
authors: Department of Molecular Genetics and Microbiology, Stony Brook University, Stony Brook NY, USA.
authors: Nicholas
authors: N
authors: Carpino
authors: Department of Biomedical Science and Human Oncology, Hygiene Section, University of Bari Bari, Italy.
authors: Maria T
authors: MT
authors: Montagna
authors: Department of Physiology and Biophysics, Stony Brook University, Stony Brook NY, USA.
authors: Chiara
authors: C
authors: Luberto
authors: Department of Molecular Genetics and Microbiology, Stony Brook University, Stony Brook NY, USA.
authors: Maurizio
authors: M
authors: Del Poeta
keywords: gene expression; glycolipid; immunosuppression; vaccine development; yeast genetics