A family of glycosylphosphatidylinositol-linked aspartyl proteases is required for virulence of Candida glabrata

Candida glabrata is a yeast pathogen of humans. We have established a tissue culture model to analyze the interaction of C. glabrata with macrophages. Transcript profiling of yeast ingested by macrophages reveals global changes in metabolism as well as increased expression of a gene family (YPS genes) encoding extracellular glycosylphosphatidylinositol-linked aspartyl proteases. Eight of these YPS genes are found in a cluster that is unique to C. glabrata. Genetic analysis shows that the C. glabrata YPS genes are required for cell wall integrity, adherence to mammalian cells, survival in macrophages and virulence. By monitoring the processing of a cell wall adhesin, Epa1, we also show that Yps proteases play an important role in cell wall re-modeling by removal and release of glycosylphosphatidylinositol-anchored cell wall proteins.