Open AccessFluconazole Alters the Polysaccharide Capsule of Cryptococcus gattii and Leads to Distinct Behaviors in Murine Cryptococcosis
Author(s) -
Julliana Ribeiro Alves Santos,
Rodrigo Assunção Holanda,
Susana Frasés,
Mayara Bravim,
Glaucy Rodrigues de Araújo,
Patrícia Campi Santos,
Marliete Carvalho Costa,
Maira Juliana Andrade Ribeiro,
Gabriella Freitas Ferreira,
Ludmila Matos Baltazar,
Aline Silva de Miranda,
Danilo Bretas de Oliveira,
Glaucy Rodrigues de Araújo,
Alide Caroline Lima Fontes,
Ludmila Ferreira Gouveia,
Maria Aparecida de Resende Stoianoff,
Jônatas Santos Abrahão,
Tatiane Alves da Paixão,
Danielle G. Souza,
Danielle Anjos dos Santos
Publication year - 2014
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0112669
Subject(s) - cryptococcosis , cryptococcus gattii , fluconazole , biology , cryptococcus neoformans , microbiology and biotechnology , azole , virulence , mycosis , immunology , antifungal , gene , biochemistry
Cryptococcus gattii is an emergent human pathogen. Fluconazole is commonly used for treatment of cryptococcosis, but the emergence of less susceptible strains to this azole is a global problem and also the data regarding fluconazole-resistant cryptococcosis are scarce. We evaluate the influence of fluconazole on murine cryptococcosis and whether this azole alters the polysaccharide (PS) from cryptococcal cells. L27/01 strain of C. gattii was cultivated in high fluconazole concentrations and developed decreased drug susceptibility. This phenotype was named L27/01 F , that was less virulent than L27/01 in mice. The physical, structural and electrophoretic properties of the PS capsule of L27/01 F were altered by fluconazole. L27/01 F presented lower antiphagocytic properties and reduced survival inside macrophages. The L27/01 F did not affect the central nervous system, while the effect in brain caused by L27/01 strain began after only 12 hours. Mice infected with L27/01 F presented lower production of the pro-inflammatory cytokines, with increased cellular recruitment in the lungs and severe pulmonary disease. The behavioral alterations were affected by L27/01, but no effects were detected after infection with L27/01 F . Our results suggest that stress to fluconazole alters the capsule of C. gattii and influences the clinical manifestations of cryptococcosis.