Research SummaryCharacterization of glycosylphosphatidylinositol-linked aspartyl proteases in Candida glabrata: role in pathogenicity
Candida species, benign residents of mucosal surfaces and the gut in healthy individuals, are the fourth most common blood stream pathogens. Among Candida species, prevalence of Candida glabrata is on the rise, and it accounts for up to 30% of Candida bloodstream infections. It is also a common etiologic agent of mucosal and urinary tract infections. Treatment of C. glabrata infections is particularly challenging as C. glabrata inherently is less susceptible to widely-used azole antifungals. Development of any new therapy requires an in-depth understanding of pathogen products that facilitate infection of host tissues. Our recent work has demonstrated a pivotal role for a family of eleven glycosylphosphatidylinositol-linked aspartyl proteases, also known as yapsins, in several cellular processes including pH and vacuole homeostasis, cell wall remodeling, intracellular survival and virulence in C. glabrata. Here, we propose to uncover the mechanisms that regulate the expression and the activity of C. glabrata yapsins. We will conduct a systematic analysis to identify yeast and mammalian substrates of yapsins, decipher their physiological functions, and examine environmental cue-dependent transcriptional regulation of yapsin-encoding genes in both clinical and culture model system contexts. Our work will aid fungal pathogenesis research and may identify new targets for therapeutic research.
Figure Legend: Schematic illustration summarizing our current research on physiology and pathogenesis of Candida glabrata. 'W', 'M' and 'YPS' refer to wild-type, mutant and yapsins, respectively.