Journal
PLOS ONE
Volume 9, Issue 11, Pages -Publisher
PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.pone.0112669
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Funding
- Fundacao de Amparo a Pesquisa do Estado de Minas Gerais (FAPEMIG)
- Conselho Nacional de Pesquisa (CNPq)
- Pro-Reitoria de Pesquisa da Universidade Federal de Minas Gerais (UFMG)
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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.
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