The Identification of Gene Duplication and the Role of Secreted Aspartyl Proteinase 1 in Candida parapsilosis Virulence

In this study, we analyzed the role of Candida parapsilosis-secreted aspartyl proteinase isoenzyme 1 (SAPP1) in virulence. The in silico analysis of SAPP1 sequence revealed a 2871 base pair-duplicated region (SAPP1a and SAPP1b) in the genome of C. parapsilosis. We generated homozygous delta delta sapp1a, delta delta sapp1b, and delta delta sapp1a-delta delta sapp1b mutants. Notably, Sapp1 production in an inducer medium was reduced by approximately 50% in the delta delta sapp1a and delta delta sapp1b mutants, but the other validated SAPP gene (SAPP2) was not affected. In contrast, Sapp2 production was increased in the delta delta sapp1a-delta delta sapp1b mutant relative to wild-type (WT) yeast. The delta delta sapp1a-delta delta sapp1b strain was hypersusceptible to human serum and was attenuated in its capacity to damage host-effector cells. The phagocytosis and killing of delta delta sapp1a-delta delta sapp1b yeasts by human peripheral blood mononuclear cells (PBMCs) and PBMC-derived macrophages (PBMC-DM) was significantly enhanced relative to WT. Phagolysosomal fusion in PBMC-DMs occurred more than twice as frequently with ingested delta delta sapp1a-delta delta sapp1b yeast cells compared with WT.