Azole resistance by loss of function of the sterol Δ⁵,⁶-desaturase gene (ERG3) in Candida albicans does not necessarily decrease virulence.

ABSTRACT: The inactivation of ERG3, a gene encoding sterol Δ⁵,⁶-desaturase (essential for ergosterol biosynthesis), is a known mechanism of in vitro resistance to azole antifungal drugs in the human pathogen Candida albicans. ERG3 inactivation typically results in loss of filamentation and attenuated virulence in animal models of disseminated candidiasis. In this work, we identified a C. albicans clinical isolate (VSY2) with high-level resistance to azole drugs in vitro and an absence of ergosterol but normal filamentation. Sequencing of ERG3 in VSY2 revealed a double base deletion leading to a premature stop codon and thus a nonfunctional enzyme. The reversion of the double base deletion in the mutant allele (erg3-1) restored ergosterol biosynthesis and full fluconazole susceptibility in VSY2, conf

SUBMITTER: Vale-Silva LA 

PROVIDER: S-EPMC3318373 | biostudies-literature | 2012 Apr

REPOSITORIES: biostudies-literature