Secreted Aspartate Proteinases (Sap) are among those factors of the human pathogen Candida albicans, which promote infections in the immunocompromised host. Sap isoenzymes are encoded by at least nine different genes (SAP1-9), which are differentially regulated in vitro. RT-PCR analysis during experimental infections and from patient samples confirmed the expression of SAP genes in vivo. However, while Sap2 is the dominant isoenzyme under culture conditions, other SAP genes are also expressed during infections. In order to investigate the role of single isoenzymes during the pathogenesis of candidosis, mutants were produced which harbour deletions in SAP1, SAP2, SAP3 and SAP4-6. Although only SAP2 and SAP4-6 mutants showed a strong reduction of proteolytic activity in vitro, all SAP mutants were significantly attenuated in systemic infections. In addition, SAP2, SAP3 and SAP4-6 mutants were clearly more sensitive to neutrophilic leucocytes compared to the wild type SC5314. These investigations show that several proteinase isoenzymes are likely to be involved in the pathogenesis of candidosis.
