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Inactivation of sterol Delta5,6-desaturase attenuates virulence in Candida albicans.


ABSTRACT: Two clinical Candida albicans isolates that exhibited high-level resistance to azoles and modest decreases in susceptibility to amphotericin B were cultured from unrelated patients. Both isolates harbored homozygous nonsense mutations in ERG3, which encodes an enzyme, sterol Delta5,6-desaturase, involved in ergosterol synthesis. Extraction and analysis of the sterols from both isolates confirmed the absence of sterol Delta5,6-desaturase activity. Although the loss of sterol Delta5,6-desaturase activity is known to confer resistance to azoles, this mechanism of resistance has rarely been seen in clinical isolates, suggesting that such mutants are at a competitive disadvantage. To test this hypothesis, the virulence of the erg3 mutants was assayed by using a mouse systemic infection model. T

SUBMITTER: Chau AS 

PROVIDER: S-EPMC1195422 | biostudies-literature | 2005 Sep

REPOSITORIES: biostudies-literature