WHAT ARE THE FUNCTIONS OF 6 DIFFERENT GENES ENCODING SECRETED PROTEINASES IN CANDIDA-ALBICANS

Secreted Aspartat Proteinases (Sap) are among those factors of the hum an pathogen Candida albicans, which promote infections in the immunoco mpromised host. Sap isoenzymes are encoded by at least nine different genes (SAP1-9), which are differentially regulated in vitro. RT-PCR an alysis during experimental infections and from patient samples confirm ed the expression of SAP genes in vivo. However, while Sap2 is the dom inant isoenzyme under culture conditions, other SAP genes are also exp ressed during infections. In order to investigate the role of single i soenzymes during the pathogenesis of candidosis, mutants were produced which habour deletions in SAP1, SAP2, SAP3 and SAP4-6. Although only SAP2 and SAP4-6 mutants showed a strong reduction of proteolytic activ ity in vitro, all SAP mutants were significantly attenuated in systemi c infections. In addition, SAP2, SAP3 and SAP4-6 mutants were clearly more sensitive to neutrophilic leucozytes compared to the wild type SC 5314. These investigations show that several proteinase isoenzymes are likely to be involved in the pathogenesis of candidosis.