Secreted aspartic protease (SAP)

Secreted aspartic proteases (SAPs) are a family of ten distinct enzymes (SAP1–10) produced by the opportunistic fungal pathogen Candida albicans to facilitate host colonization and infection [1]. These enzymes function by cleaving a variety of host substrates, including structural proteins like collagen, keratin, and laminin, as well as immunological proteins such as secretory IgA and complement components [2]. This proteolytic activity is essential for nutrient acquisition, tissue penetration, and evasion of the host immune response [3]. SAPs are differentially expressed depending on the site of infection and the environmental conditions, with SAP1–3 typically associated with mucosal infections and SAP4–6 linked to systemic disease [1, 5]. Due to their pivotal role in fungal virulence, SAPs are recognized as significant therapeutic targets for the development of novel antifungal agents [4]. Clinical observations have shown that HIV protease inhibitors, such as ritonavir and indinavir, can directly inhibit SAP activity, contributing to the decline of candidiasis in HIV-positive patients [4]. However, the development of SAP-specific inhibitors is complicated by the structural homology between different SAP isoforms and the potential for cross-reactivity with human aspartic proteases like pepsin or cathepsin D [1].

Other names

CandidapepsinSecreted aspartyl proteinaseSecreted aspartate proteinaseAspartic proteinaseSAP1-10Candida albicans aspartic protease

Competitive inhibition of the aspartic protease active site, preventing the cleavage of host proteins and inhibiting fungal virulence, adherence, and growth [1, 4].