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Disruption of the Candida albicans ATC1 gene encoding a cell-linked acid trehalase decreases hypha formation and infectivity without affecting resistance to oxidative stress

¹ Área de Microbiología, Facultad de Biología, Universidad de Murcia, E-30071 Murcia, Spain
² Departamento de Microbiología y Ecología, Universidad de Valencia, E-46100 Burjassot, Valencia, Spain
³ Departamento de Bioquímica y Biología Molecular B e Inmunología, Universidad de Murcia, E-30071 Murcia, Spain

Correspondence
Juan-Carlos Argüelles
arguelle{at}um.es

In Candida albicans, the ATC1 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 atc1/atc1 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 atc1 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 H₂O₂), which are relevant during in vivo 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 H₂O₂), whereas superoxide dismutase was inhibited dramatically by H₂O₂, where a more marked decrease was observed in atc1 cells. In turn, the atc1 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 ATC1 gene in dimorphism and infectivity, but also that an interconnection between stress resistance, dimorphic conversion and virulence in C. albicans may be reconsidered. They also support the hypothesis that Atc1p is not involved in the physiological hydrolysis of endogenous trehalose.

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