Role of AFR1, an ABC transporter-encoding gene, in the in vivo response to fluconazole and virulence of Cryptococcus neoformans.

ABSTRACT: We have recently demonstrated that upregulation of the ATP binding cassette (ABC) transporter-encoding gene AFR1 in Cryptococcus neoformans is involved in the in vitro resistance to fluconazole of this yeast. In the present study, we investigated the role of AFR1 in the in vivo response to fluconazole in a mouse model of systemic cryptococcosis. Mice were infected with a wild-type fluconazole-susceptible strain of C. neoformans, strain BPY22; an afr1 mutant, BPY444, which displayed hypersusceptibility to fluconazole in vitro; or an AFR1-overexpressing strain, BPY445, which exhibited in vitro resistance to the drug. In each of the three groups, infected animals were randomly assigned to fluconazole treatment or untreated-control subgroups. As expected, fluconazole prolonged survival and red

SUBMITTER: Sanguinetti M 

PROVIDER: S-EPMC1360305 | biostudies-literature | 2006 Feb

REPOSITORIES: biostudies-literature