Open AccessThe ABC transporter‐encoding gene AFR1 affects the resistance of Cryptococcus neoformans to microglia‐mediated antifungal activity by delaying phagosomal maturation
Author(s) -
Orsi Carlotta Francesca,
Colombari Bruna,
Ardizzoni Andrea,
Peppoloni Samuele,
Neglia Rachele,
Posteraro Brunella,
Morace Giulia,
Fadda Giovanni,
Blasi Elisabetta
Publication year - 2009
Publication title -
fems yeast research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.991
H-Index - 92
eISSN - 1567-1364
pISSN - 1567-1356
DOI - 10.1111/j.1567-1364.2008.00470.x
Subject(s) - cryptococcus neoformans , biology , microbiology and biotechnology , microglia , virulence , fluconazole , phagosome , gene , mutant , downregulation and upregulation , efflux , yeast , cryptococcosis , atp binding cassette transporter , phagocytosis , cryptococcus gattii , transporter , immunology , antifungal , genetics , inflammation
The pathogenic yeast Cryptococcus neoformans has evolved several strategies to survive within phagocytes. Recently, it has been demonstrated that upregulation of the ATP binding cassette transporter‐encoding gene antifungal resistance 1 ( AFR1 ) is important not only for determining the resistance of C. neoformans to fluconazole but also in influencing fungal virulence. In the present study, we showed that the fluconazole‐resistant AFR1‐ overexpressing mutant strain was not sensitive to microglia‐mediated anticryptococcal activity, as compared with the fluconazole‐susceptible isogenic strains, the wild type and the afr1 Δ mutant. Interestingly, although the three strains were phagocytosed to a similar extent, reduced acidification and delayed maturation were observed in phagosomes containing the AFR1 ‐overexpressing strain with respect to the others. These findings provide the first evidence that upregulation of the AFR1 gene affects C. neoformans –microglia interplay, adding insights to the complexity of cryptococcal virulence and to its unexpected link with azole resistance.