S8.3d Characterization of glycosylphosphatidylinositol-linked aspartyl proteases in Candida glabrata: Role in pathogenicity

S8.3 HOW THE FUNGAL CELL WALL GLYCAN CAN MODULATE THE IMMUNE RESPONSE?, SEPTEMBER 23, 2022, 3:00 PM - 4:30 PM: : Candida glabrata is the second to fourth most common yeast pathogen found in Candida bloodstream infections, depending upon the geographical location. C. glabrata, which belongs to the Nakaseomyces clade, possesses a distinct set of virulence attributes which include the ability to survive and proliferate in macrophages, adhere to biotic and abiotic surfaces and survive a wide range of stresses. Our research is focused on unveiling the strategies that C. glabrata employs to survive the nutrient-poor hostile host environment and evade host immune response. Toward this end, we are delineating the cellular processes, that are regulated by the family of 11 putative glycosylphosphatidylinositol-linked, cell surface-associated aspartyl proteases (CgYapsins, CgYps1-11). We have recently characterized the secretome of C. glabrata wild-type and aspartyl protease-deficient mutant strains, and showed that the GPI-anchored aspartyl proteases are both bonafide constituents and key modulators of the C. glabrata secretome. Further, besides elucidating the role of CgYapsins in the suppression of the host pro-inflammatory immune response, we have identified the flavodoxin-like protein CgPst2 as a substrate of the CgYps1 protease and demonstrated that the CgYps1-mediated cleavage of CgPst2 is pivotal to oligomerization and activity, and functions of CgPst2 in quinone detoxification. These findings underscoring the importance of multifunctional CgYapsins in the physiology and pathogenesis of C. glabrata will be presented.