Fluconazole alters the polysaccharide capsule of Cryptococcus gattii and leads to distinct behaviors in murine Cryptococcosis.
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 f...
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| Format: | Article |
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Public Library of Science (PLoS)
2014-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC4231059?pdf=render |
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| author | Julliana Ribeiro Alves Santos Rodrigo Assunção Holanda Susana Frases Mayara Bravim Glauber de S Araujo Patrícia Campi Santos Marliete Carvalho Costa Maira Juliana Andrade Ribeiro Gabriella Freitas Ferreira Ludmila Matos Baltazar Aline Silva Miranda Danilo Bretas Oliveira Carolina Maria Araújo Santos Alide Caroline Lima Fontes Ludmila Ferreira Gouveia Maria Aparecida Resende-Stoianoff Jonatas Santos Abrahão Antônio Lúcio Teixeira Tatiane Alves Paixão Danielle G Souza Daniel Assis Santos |
| author_facet | Julliana Ribeiro Alves Santos Rodrigo Assunção Holanda Susana Frases Mayara Bravim Glauber de S Araujo Patrícia Campi Santos Marliete Carvalho Costa Maira Juliana Andrade Ribeiro Gabriella Freitas Ferreira Ludmila Matos Baltazar Aline Silva Miranda Danilo Bretas Oliveira Carolina Maria Araújo Santos Alide Caroline Lima Fontes Ludmila Ferreira Gouveia Maria Aparecida Resende-Stoianoff Jonatas Santos Abrahão Antônio Lúcio Teixeira Tatiane Alves Paixão Danielle G Souza Daniel Assis Santos |
| author_sort | Julliana Ribeiro Alves Santos |
| collection | DOAJ |
| description | 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 L27/01F, that was less virulent than L27/01 in mice. The physical, structural and electrophoretic properties of the PS capsule of L27/01F were altered by fluconazole. L27/01F presented lower antiphagocytic properties and reduced survival inside macrophages. The L27/01F 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 L27/01F 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 L27/01F. Our results suggest that stress to fluconazole alters the capsule of C. gattii and influences the clinical manifestations of cryptococcosis. |
| first_indexed | 2024-04-13T17:42:39Z |
| format | Article |
| id | doaj.art-a5b278a0915c437a9b64230269bbde16 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-04-13T17:42:39Z |
| publishDate | 2014-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-a5b278a0915c437a9b64230269bbde162022-12-22T02:37:07ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-01911e11266910.1371/journal.pone.0112669Fluconazole alters the polysaccharide capsule of Cryptococcus gattii and leads to distinct behaviors in murine Cryptococcosis.Julliana Ribeiro Alves SantosRodrigo Assunção HolandaSusana FrasesMayara BravimGlauber de S AraujoPatrícia Campi SantosMarliete Carvalho CostaMaira Juliana Andrade RibeiroGabriella Freitas FerreiraLudmila Matos BaltazarAline Silva MirandaDanilo Bretas OliveiraCarolina Maria Araújo SantosAlide Caroline Lima FontesLudmila Ferreira GouveiaMaria Aparecida Resende-StoianoffJonatas Santos AbrahãoAntônio Lúcio TeixeiraTatiane Alves PaixãoDanielle G SouzaDaniel Assis SantosCryptococcus 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 L27/01F, that was less virulent than L27/01 in mice. The physical, structural and electrophoretic properties of the PS capsule of L27/01F were altered by fluconazole. L27/01F presented lower antiphagocytic properties and reduced survival inside macrophages. The L27/01F 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 L27/01F 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 L27/01F. Our results suggest that stress to fluconazole alters the capsule of C. gattii and influences the clinical manifestations of cryptococcosis.http://europepmc.org/articles/PMC4231059?pdf=render |
| spellingShingle | Julliana Ribeiro Alves Santos Rodrigo Assunção Holanda Susana Frases Mayara Bravim Glauber de S Araujo Patrícia Campi Santos Marliete Carvalho Costa Maira Juliana Andrade Ribeiro Gabriella Freitas Ferreira Ludmila Matos Baltazar Aline Silva Miranda Danilo Bretas Oliveira Carolina Maria Araújo Santos Alide Caroline Lima Fontes Ludmila Ferreira Gouveia Maria Aparecida Resende-Stoianoff Jonatas Santos Abrahão Antônio Lúcio Teixeira Tatiane Alves Paixão Danielle G Souza Daniel Assis Santos Fluconazole alters the polysaccharide capsule of Cryptococcus gattii and leads to distinct behaviors in murine Cryptococcosis. PLoS ONE |
| title | Fluconazole alters the polysaccharide capsule of Cryptococcus gattii and leads to distinct behaviors in murine Cryptococcosis. |
| title_full | Fluconazole alters the polysaccharide capsule of Cryptococcus gattii and leads to distinct behaviors in murine Cryptococcosis. |
| title_fullStr | Fluconazole alters the polysaccharide capsule of Cryptococcus gattii and leads to distinct behaviors in murine Cryptococcosis. |
| title_full_unstemmed | Fluconazole alters the polysaccharide capsule of Cryptococcus gattii and leads to distinct behaviors in murine Cryptococcosis. |
| title_short | Fluconazole alters the polysaccharide capsule of Cryptococcus gattii and leads to distinct behaviors in murine Cryptococcosis. |
| title_sort | fluconazole alters the polysaccharide capsule of cryptococcus gattii and leads to distinct behaviors in murine cryptococcosis |
| url | http://europepmc.org/articles/PMC4231059?pdf=render |
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