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.