1887

Abstract

This paper describes (i) the expression profile of the methionine synthase gene () in the human pathogenic fungus and (ii) the phenotypes of a mutant. In contrast to the gene, which showed no significant change in expression in any environmental condition tested, the gene showed a substantial induction in response to methionine and a dramatic transcriptional induction in response to homocysteine. Like a mutant, the mutant was a methionine auxotroph. However, relative to a mutant, the mutant grew very slowly and was less heat-shock resistant. In contrast to a mutant, the mutant lost viability when starved of methionine, and it was deficient in capsule formation. Like a mutant, the mutant was avirulent. In contrast to a mutant, the mutant was hypersensitive to fluconazole and to the calcineurin inhibitors FK506 and cyclosporin A. A synergistic fungicidal effect was also found between each of these drugs and . The phenotypic differences between the and mutants may be due to the accumulation in mutants of homocysteine, a toxic metabolic intermediate that inhibits sterol biosynthesis.

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2004-09-01
2019-11-13
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