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

Abstract

Candida glabratais a yeast pathogen of humans. We have established a tissue culture model to analyze the interaction ofC. glabratawith macrophages. Transcript profiling of yeast ingested by macrophages reveals global changes in metabolism as well as increased expression of a gene family (YPSgenes) encoding extracellular glycosylphosphatidylinositol-linked aspartyl proteases. Eight of theseYPSgenes are found in a cluster that is unique toC. glabrata. Genetic analysis shows that theC. glabrata YPSgenes 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.