Two clinical @entity5132 isolates that exhibited high-level resistance to @entity8201 and modest decreases in susceptibility to @entity2379 were cultured from unrelated @entity1 . Both isolates harbored homozygous nonsense mutations in @entity29945 , which encodes an enzyme, @entity5068 @entity846 ,6-desaturase, involved in @entity12364 synthesis. Extraction and analysis of the @entity3150 from both isolates confirmed the absence of @entity5068 @entity846 ,6-desaturase activity. Although the loss of @entity5068 @entity846 ,6-desaturase activity is known to confer resistance to @entity8201 , 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 @entity29945 mutants was assayed by using a @entity19 @entity281 model. The mutants were significantly less virulent than the wild-type comparator strains. However, the kidney fungal burdens in @entity19 infected with the @entity29945 mutants were similar to those in @entity19 infected with the wild-type strains. Similar results were obtained by using a laboratory-generated homozygous @entity29945 deletion mutant (D. Sanglard et al., Antimicrob. Agents Chemother. 47:2404-2412, 2003). Reintroduction of a wild-type @entity29945 allele into the homozygous deletion mutant restored virulence, @entity12364 synthesis, and susceptibility to @entity8201 , confirming that these phenotypic changes were solely due to the inactivation of @entity29945 .

Inactivation of @entity5068 @entity846 ,6-desaturase attenuates virulence in XXXX .

@entity1 :: ('9606', 'Species') :: ['patients'] @entity29945 :: ('170738(Tax:10090)', 'Gene') :: ['erg3', 'ERG3', 'Erg3p'] @entity846 :: ('|DEL||5', 'DNAMutation') :: ['Delta5'] @entity12364 :: ('MESH:D004875', 'Chemical') :: ['ergosterol'] @entity2379 :: ('MESH:D000666', 'Chemical') :: ['amphotericin B'] @entity19 :: ('10090', 'Species') :: ['mice', 'mouse'] @entity5132 :: ('5476', 'Species') :: ['Candida albicans'] @entity281 :: ('MESH:D007239', 'Disease') :: ['systemic infection'] @entity3150 :: ('MESH:D013261', 'Chemical') :: ['sterols'] @entity5068 :: ('CHEBI:15889', 'Chemical') :: ['sterol'] @entity8201 :: ('MESH:D001393', 'Chemical') :: ['azoles']
@entity5132 :: (5476,Species) :: ['Candida albicans']
