1887

Abstract

In , the gene, encoding a cell wall-associated acid trehalase, has been considered as a potentially interesting target in the search for new antifungal compounds. A phenotypic characterization of the double disruptant Δ/Δ mutant showed that it was unable to grow on exogenous trehalose as sole carbon source. Unlike actively growing cells from the parental strain (CAI4), the Δ null mutant displayed higher resistance to environmental insults, such as heat shock (42 °C) or saline exposure (0.5 M NaCl), and to both mild and severe oxidative stress (5 and 50 mM HO), which are relevant during infections. Parallel measurements of intracellular trehalose and trehalose-metabolizing enzymes revealed that significant amounts of the disaccharide were stored in response to thermal and oxidative challenge in the two cell types. The antioxidant activities of catalase and glutathione reductase were triggered by moderate oxidative exposure (5 mM HO), whereas superoxide dismutase was inhibited dramatically by HO, where a more marked decrease was observed in Δ cells. In turn, the Δ mutant exhibited a decreased capacity of hypha and pseudohypha formation tested in different media. Finally, the homozygous null mutant in a mouse model of systemic candidiasis displayed strongly reduced pathogenicity compared with parental or heterozygous strains. These results suggest not only a novel role for the gene in dimorphism and infectivity, but also that an interconnection between stress resistance, dimorphic conversion and virulence in may be reconsidered. They also support the hypothesis that Atc1p is not involved in the physiological hydrolysis of endogenous trehalose.

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2007-05-01
2020-04-10
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