AUTHOR=Rella Antonella , Mor Visesato , Farnoud Amir M. , Singh Ashutosh , Shamseddine Achraf A. , Ivanova Elitza , Carpino Nicholas , Montagna Maria T. , Luberto Chiara , Del Poeta Maurizio 

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

JOURNAL=Frontiers in Microbiology

VOLUME=6

YEAR=2015

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2015.00836

DOI=10.3389/fmicb.2015.00836

ISSN=1664-302X

ABSTRACT=<p>Cryptococcosis caused by <italic>Cryptococcus neoformans</italic> and <italic>Cryptococcus gattii</italic> 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 <italic>C. neoformans</italic> 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<italic>sgl1</italic>) 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 <italic>C. neoformans</italic> or <italic>C. gattii</italic>. The immunity induced by the Δ<italic>sgl1</italic> strain is not CD4<sup>+</sup> T-cells dependent. Immunocompromised mice, which lack CD4<sup>+</sup> T-cells, are able to control the infection by Δ<italic>sgl1</italic> and acquire immunity against the challenge by wild-type <italic>C. neoformans</italic> following vaccination with the Δ<italic>sgl1</italic> strain. These findings are particularly important in the context of HIV/AIDS immune deficiency and suggest that the Δ<italic>sgl1</italic> strain might provide a potential vaccination strategy against cryptococcosis.</p>