DEGRADATION OF HUMAN SUBENDOTHELIAL EXTRACELLULAR-MATRIX BY PROTEINASE-SECRETING CANDIDA-ALBICANS

Candida albicans infections in severely immunocompromized patients are not confined to mucosal surfaces; instead the fungus can invade throu gh epithelial and endothelial layers into the bloodstream and spread t o other organs, causing disseminated infections with often fatal outco me. We investigated whether secretion of the C. albicans acid proteina se facilitates invasion into deeper tissues by degrading the subendoth elial basement membrane. After cultivation under conditions that induc e the secretion of the acid proteinase, C. albicans degraded radioacti vely metabolically labeled extracellular matrix proteins from a human endothelial cell line. The degradation was inhibited in the presence o f pepstatin A, an inhibitor of acid proteinases. Pepstatin A-sensitive degradation of the soluble and immobilized extracellular matrix prote ins fibronectin and laminin by proteinase-producing C. albicans was al so detected, whereas no degradation was observed when the expression o f the acid proteinase was repressed. Our results demonstrate that the C. albicans acid proteinase degrades human subendothelial extracellula r matrix; this may be of importance in the penetration of C. albicans into circulation and deep organs.