Secreted Aspartic Proteinases: Key Factors in Candida Infections and Host-Pathogen Interactions

Abstract

Extracellular proteases are key factors contributing to the virulence of pathogenic fungi from the genus Candida. Their proteolytic activities are crucial for extracting nutrients from the external environment, degrading host defenses, and destabilizing the internal balance of the human organism. Currently, the enzymes most frequently described in this context are secreted aspartic proteases (Saps). This review comprehensively explores the multifaceted roles of Saps, highlighting their importance in biofilm formation, tissue invasion through the degradation of extracellular matrix proteins and components of the coagulation cascade, modulation of host immune responses via impairment of neutrophil and monocyte/macrophage functions, and their contribution to antifungal resistance. Additionally, the diagnostic challenges associated with Candida infections and the potential of Saps as biomarkers were discussed. Furthermore, we examined the prospects of developing vaccines based on Saps and the use of protease inhibitors as adjunctive therapies for candidiasis. Given the complex biology of Saps and their central role in Candida pathogenicity, a multidisciplinary approach may pave the way for innovative diagnostic strategies and open new opportunities for innovative clinical interventions against candidiasis.

Saps1–3 Antigens in Candida albicans: Differential Modulation Following Exposure to Soluble Proteins, Mammalian Cells, and Infection in Mice

“…A similar compensatory strategy was observed when C. albicans cells were incubated with human IgG. These results may suggest distinct biological regulations promoted by soluble proteins in C. albicans cells, as the secretion of Saps is a key mechanism for evading the host’s immune system by Candida species [ 52 ]. Furthermore, Saps play a role in the progression of candidiasis by aiding Candida yeasts in degrading hemoglobin, which is a crucial event for acquiring iron, facilitating yeast cell proliferation during systemic infection [ 53 ].…”