Title: Disruption of the Candida albicans TPS2 gene encoding trehalose-6-phosphate phosphatase decreases infectivity without affecting hypha formation
Authors: Van Dijck, Patrick ×
De Rop, Larissa
Szlufcik, Karolina
Van Ael, Elke
Thevelein, Johan #
Issue Date: Apr-2002
Publisher: Amer soc microbiology
Series Title: Infection and immunity vol:70 issue:4 pages:1772-1782
Abstract: Deletion of trehalose-6-phosphate phosphatase, encoded by TPS2, in Saccharomyces cerevisiae results in accumulation of trehalose-6-phosphate (Tre6P) instead of trehalose under stress conditions. Since trehalose is an important stress protectant and Tre6P accumulation is toxic, we have investigated whether Tre6P phosphatase could be a useful target for antifungals in Candida albicans. We have cloned the C. albicans TPS2 (CaTPS2) gene and constructed heterozygous and homozygous deletion strains. As in S. cerevisiae, complete inactivation of Tre6P phosphatase in C. albicans results in 50-fold hyperaccumulation of Tre6P, thermosensitivity, and rapid death of the cells after a few hours at 44 C. As opposed to inactivation of TCe6P synthase by deletion of CaTPS1, deletion of CaTPS2 does not affect hypha formation on a solid glucose-containing medium. In spite of this, virulence of the homozygous deletion mutant is strongly reduced in a mouse model of systemic infection. The pathogenicity of the heterozygous deletion mutant is similar to that of the wild-type strain. CaTPS2 is a new example of a gene not required for growth under standard conditions but required for pathogenicity in a host. Our results suggest that Tre6P phosphatase may serve as a potential target for antifungal drugs. Neither Tre6P phosphatase nor its substrate is present in mammals, and assay of the enzymes is simple and easily automated for high-throughput screening.
ISSN: 0019-9567
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Molecular Microbiology and Biotechnology Section - miscellaneous
Laboratory of Lipid Biochemistry and Protein Interactions
Exercise Physiology Research Group
× corresponding author
# (joint) last author

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