Cargando…

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

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. I...

Descripción completa

Detalles Bibliográficos
Autores principales: Rella, Antonella, Mor, Visesato, Farnoud, Amir M., Singh, Ashutosh, Shamseddine, Achraf A., Ivanova, Elitza, Carpino, Nicholas, Montagna, Maria T., Luberto, Chiara, Del Poeta, Maurizio
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4531891/
https://www.ncbi.nlm.nih.gov/pubmed/26322039
http://dx.doi.org/10.3389/fmicb.2015.00836
_version_ 1782385130130636800
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
author_facet Rella, Antonella
Mor, Visesato
Farnoud, Amir M.
Singh, Ashutosh
Shamseddine, Achraf A.
Ivanova, Elitza
Carpino, Nicholas
Montagna, Maria T.
Luberto, Chiara
Del Poeta, Maurizio
author_sort Rella, Antonella
collection PubMed
description 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.
format Online
Article
Text
id pubmed-4531891
institution National Center for Biotechnology Information
language English
publishDate 2015
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-45318912015-08-28 Role of Sterylglucosidase 1 (Sgl1) on the pathogenicity of Cryptococcus neoformans: potential applications for vaccine development Rella, Antonella Mor, Visesato Farnoud, Amir M. Singh, Ashutosh Shamseddine, Achraf A. Ivanova, Elitza Carpino, Nicholas Montagna, Maria T. Luberto, Chiara Del Poeta, Maurizio Front Microbiol Microbiology 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. Frontiers Media S.A. 2015-08-11 /pmc/articles/PMC4531891/ /pubmed/26322039 http://dx.doi.org/10.3389/fmicb.2015.00836 Text en Copyright © 2015 Rella, Mor, Farnoud, Singh, Shamseddine, Ivanova, Carpino, Montagna, Luberto and Del Poeta. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Microbiology
Rella, Antonella
Mor, Visesato
Farnoud, Amir M.
Singh, Ashutosh
Shamseddine, Achraf A.
Ivanova, Elitza
Carpino, Nicholas
Montagna, Maria T.
Luberto, Chiara
Del Poeta, Maurizio
Role of Sterylglucosidase 1 (Sgl1) on the pathogenicity of Cryptococcus neoformans: potential applications for vaccine development
title Role of Sterylglucosidase 1 (Sgl1) on the pathogenicity of Cryptococcus neoformans: potential applications for vaccine development
title_full Role of Sterylglucosidase 1 (Sgl1) on the pathogenicity of Cryptococcus neoformans: potential applications for vaccine development
title_fullStr Role of Sterylglucosidase 1 (Sgl1) on the pathogenicity of Cryptococcus neoformans: potential applications for vaccine development
title_full_unstemmed Role of Sterylglucosidase 1 (Sgl1) on the pathogenicity of Cryptococcus neoformans: potential applications for vaccine development
title_short Role of Sterylglucosidase 1 (Sgl1) on the pathogenicity of Cryptococcus neoformans: potential applications for vaccine development
title_sort role of sterylglucosidase 1 (sgl1) on the pathogenicity of cryptococcus neoformans: potential applications for vaccine development
topic Microbiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4531891/
https://www.ncbi.nlm.nih.gov/pubmed/26322039
http://dx.doi.org/10.3389/fmicb.2015.00836
work_keys_str_mv AT rellaantonella roleofsterylglucosidase1sgl1onthepathogenicityofcryptococcusneoformanspotentialapplicationsforvaccinedevelopment
AT morvisesato roleofsterylglucosidase1sgl1onthepathogenicityofcryptococcusneoformanspotentialapplicationsforvaccinedevelopment
AT farnoudamirm roleofsterylglucosidase1sgl1onthepathogenicityofcryptococcusneoformanspotentialapplicationsforvaccinedevelopment
AT singhashutosh roleofsterylglucosidase1sgl1onthepathogenicityofcryptococcusneoformanspotentialapplicationsforvaccinedevelopment
AT shamseddineachrafa roleofsterylglucosidase1sgl1onthepathogenicityofcryptococcusneoformanspotentialapplicationsforvaccinedevelopment
AT ivanovaelitza roleofsterylglucosidase1sgl1onthepathogenicityofcryptococcusneoformanspotentialapplicationsforvaccinedevelopment
AT carpinonicholas roleofsterylglucosidase1sgl1onthepathogenicityofcryptococcusneoformanspotentialapplicationsforvaccinedevelopment
AT montagnamariat roleofsterylglucosidase1sgl1onthepathogenicityofcryptococcusneoformanspotentialapplicationsforvaccinedevelopment
AT lubertochiara roleofsterylglucosidase1sgl1onthepathogenicityofcryptococcusneoformanspotentialapplicationsforvaccinedevelopment
AT delpoetamaurizio roleofsterylglucosidase1sgl1onthepathogenicityofcryptococcusneoformanspotentialapplicationsforvaccinedevelopment