Secreted aspartic proteinase (Sap) activity contributes to tissue damage in a model of human oral candidosis

摘要: Secreted aspartic proteinases (Saps) are important virulence factors during Candida albicans mucosal or disseminated infections. A differential expression of individual SAP genes has been shown previously in a model oral candidosis based on reconstituted human epithelium (RHE), and the cavity patients. In this study, ultrastructural localization distinct groups Sap isoenzymes expressed RHE infection was by immunoelectron microscopy using specific polyclonal antibodies directed against gene products SAP1-3 SAP4-6. Large amounts Sap1-3 antigen were found within C. yeast hyphal cell walls, often predominantly close contact with epithelial cells, whereas lower quantities Sap4-6 detected cells. To elucidate relevance Saps infections, we examined effect proteinase inhibitor, pepstatin A, RHE. The extent lesions caused strain SC5314 to be strongly reduced indicating that activity contributes tissue damage model. clarify which for necrosis, histology Deltasap1, Deltasap2, Deltasap3, Deltasap4-6 three Deltasap1/3 double mutants examined. Although not blocked completely these mutants, an attenuated phenotype observed each single sap null more mutants. contrast, triple mutant at least as severe those SC5314. During pattern Deltasap1 altered comparison wild-type strain. Expression SAP5 only mutant, upregulation SAP2 SAP8 transcripts These results suggest Sap1-3, but Sap4-6, contribute Furthermore, may compensate deletion certain alternative genes.