Functional Characterization of Secreted Aspartyl Proteases in Candida parapsilosis

is an emerging non- species that largely affects low-birth-weight infants and immunocompromised patients. Fungal pathogenesis is promoted by the dynamic expression of diverse virulence factors, with secreted proteolytic enzymes being linked to the establishment and progression of disease. Although secreted aspartyl proteases (Sap) are critical for pathogenicity, their role in is poorly elucidated. In the present study, we aimed to examine the contribution of genes , , and to the virulence of the species. Our results indicate that and , but not , influence adhesion, host cell damage, phagosome-lysosome maturation, phagocytosis, killing capacity, and cytokine secretion by human peripheral blood-derived macrophages. Purified Sapp1p and Sapp2p were also shown to efficiently cleave host complement component 3b (C3b) and C4b proteins and complement regulator factor H. Additionally, Sapp2p was able to cleave factor H-related protein 5 (FHR-5). Altogether, these data demonstrate the diverse, significant contributions that and make to the establishment and progression of disease by through enabling the attachment of the yeast cells to mammalian cells and modulating macrophage biology and disruption of the complement cascade. Aspartyl proteases are present in various organisms and, among virulent species, are considered major virulence factors. Host tissue and cell damage, hijacking of immune responses, and hiding from innate immune cells are the most common behaviors of fungal secreted proteases enabling pathogen survival and invasion. , an opportunistic human-pathogenic fungus mainly threatening low-birth weight neonates and children, possesses three protein-encoding genes that could contribute to the invasiveness of the species. Our results suggest that and , but not , influence host evasion by regulating cell damage, phagocytosis, phagosome-lysosome maturation, killing, and cytokine secretion. Furthermore, and also effectively contribute to complement evasion.