Cryptococcus neoformans responds to mannitol by increasing capsule size in vitro and in vivo |
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Authors: | Allan Jefferson Guimarães Susana Frases Radamés J. B. Cordero Leonardo Nimrichter Arturo Casadevall Joshua D. Nosanchuk |
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Affiliation: | 1. Departments of Medicine (Division of Infectious Diseases) and;2. Microbiology and Immunology, Albert Einstein College of Medicine of Yeshiva University, Bronx, NY, USA.;3. A.J.G. and S.F. contributed equally to this work.;4. Laboratório de Biotecnologia (LABIO), Instituto Nacional de Metrologia, Normaliza??o e Qualidade Industrial (INMETRO), Rio de Janeiro, Brazil.;5. Laboratório de Estudos integrados em Bioquímica Microbiana, Instituto de Microbiologia Professor Paulo de Góes, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil. |
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Abstract: | The polysaccharide capsule of the fungus Cryptococcus neoformans is its main virulence factor. In this study, we determined the effects of mannitol and glucose on the capsule and exopolysaccharide production. Growth in mannitol significantly increased capsular volume compared with cultivation in glucose. However, cells grown in glucose concentrations higher than 62.5 mM produced more exopolysaccharide than cells grown in mannitol. The fibre lengths and glycosyl composition of capsular polysaccharide from yeast grown in mannitol was structurally different from that of yeast grown in glucose. Furthermore, mannitol treatment of mice infected intratracheally with C. neoformans resulted in fungal cells with significantly larger capsules and the mice had reduced fungal dissemination to the brain. Our results demonstrate the capacity of carbohydrate source and concentration to modify the expression of a major virulence factor of C. neoformans. These findings may impact the clinical management of cryptococcosis. |
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