Expression of Candida albicans glutathione transferases is induced inside phagocytes and upon diverse environmental stresses

Abstract

Candida albicans has four ORFs for glutathione transferases (GSTs) of the GTT classes, and another one coding for an Omega class member. Under laboratory conditions, only GTT11 (GTT1/2 class) and GTO1 (Omega class) are expressed significantly in exponentially growing cells, particularly when these are subjected to diverse environmental stresses, including oxidative stress. They also become transitorily upregulated at the early stationary phase. Accordingly, the levels of the CaGto1 and CaGtt11 proteins increase after treatment with oxidants and upon osmotic stress, in addition to the early stationary phase. GTT11 and GTO1 transcription shows a complex dependence on the Hog1 and Cap1 factors upon different stresses. Purified CaGtt11 and CaGto1 proteins display enzyme activities similar to the Saccharomyces cerevisiae homologues. Thus, CaGtt11 has activity against standard GST substrates and is also active as peroxidase, while CaGto1 displays thiol oxidoreductase and dehydroascorbate reductase activities. Fluores- cence microscopy and subfractionation studies indicate that CaGto1 is cytosolic, while CaGtt11 is associated with a particulate fraction. Under ex vivo conditions, CaGto1 and CaGtt11 become transitorily upregulated inside macrophages and neutrophils. Under these conditions, the promoter of GTT14 (GTT1/2 class) also becomes activated. These observations point to the importance of C. albicans GSTs in the defence against phagocytes.