The ABC transporter-encoding gene AFR1 affects the resistance of Cryptococcus neoformans to microglia-mediated antifungal activity by delaying phagosomal maturation.

Abstract:

: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 afr1Delta 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.

journal_name

FEMS Yeast Res

journal_title

FEMS yeast research

authors

Orsi CF,Colombari B,Ardizzoni A,Peppoloni S,Neglia R,Posteraro B,Morace G,Fadda G,Blasi E

doi

10.1111/j.1567-1364.2008.00470.x

subject

Has Abstract

pub_date

2009-03-01 00:00:00

pages

301-10

issue

2

eissn

1567-1356

issn

1567-1364

pii

FYR470

journal_volume

9

pub_type

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