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Degradation of human subendothelial extracellular matrix by proteinase-secreting Candida albicans
J Morschhäuser1, R Virkola, T K Korhonen
1Zentrum für Infektionsforschung, University of Würzburg, Germany. j.morschhaeuser@rzbox.uni-wuerzburg.de
Abstract:
Candida albicans infections in severely immunocompromized patients are not confined to mucosal surfaces; instead the fungus can invade through epithelial and endothelial layers into the bloodstream and spread to other organs, causing disseminated infections with often fatal outcome. We investigated whether secretion of the C. albicans acid proteinase facilitates invasion into deeper tissues by degrading the subendothelial basement membrane. After cultivation under conditions that induce the secretion of the acid proteinase, C. albicans degraded radioactively metabolically labeled extracellular matrix proteins from a human endothelial cell line. The degradation was inhibited in the presence of pepstatin A, an inhibitor of acid proteinases. Pepstatin A-sensitive degradation of the soluble and immobilized extracellular matrix proteins fibronectin and laminin by proteinase-producing C. albicans was also detected, whereas no degradation was observed when the expression of the acid proteinase was repressed. Our results demonstrate that the C. albicans acid proteinase degrades human subendothelial extracellular matrix; this may be of importance in the penetration of C. albicans into circulation and deep organs.
Insights
Candida albicans secretes an acid proteinase that degrades the subendothelial basement membrane, aiding fungal invasion into the bloodstream and organs in immunocompromised patients.
Area of Science:
- Microbiology
- Mycology
- Infectious Diseases
Background:
- Candida albicans infections can disseminate from mucosal surfaces to deep organs in immunocompromised individuals.
- Fungal invasion into the bloodstream and subsequent organ spread can lead to fatal outcomes.
Purpose of the Study:
- To investigate if Candida albicans acid proteinase facilitates tissue invasion by degrading the subendothelial basement membrane.
- To determine the role of secreted acid proteinase in extracellular matrix degradation.
Main Methods:
- Cultivating Candida albicans under conditions that induce acid proteinase secretion.
- Assessing the degradation of radioactively labeled extracellular matrix proteins from human endothelial cells.
- Utilizing pepstatin A, an acid proteinase inhibitor, to evaluate degradation.
- Comparing degradation with and without repressed acid proteinase expression.
Main Results:
- Candida albicans degraded extracellular matrix proteins from human endothelial cells when acid proteinase secretion was induced.
- Degradation of fibronectin and laminin was sensitive to pepstatin A.
- No degradation occurred when acid proteinase expression was repressed.
Conclusions:
- The Candida albicans acid proteinase degrades human subendothelial extracellular matrix.
- This degradation mechanism may be crucial for Candida albicans penetration into circulation and deep organs.