Mucosal epithelial E- cadherin degradation by Candida albicans

Objectives: The invasion mechanism of Candida yeasts through the mucosal epithelium is unknown. It is believed that trauma is needed for the penetration of Candida into tissues. There are indications that the invasion may be aided also by Candida proteinases. Therefore we set out to test the ability C. albicans blastospore and hyphal associated proteinases to degrade the main mucosal epithelial adhesion protein, E-cadherin. Methods: C. albicans strains used were: reference strain CCUG 32723; clinical strain B1134; SC5314 which is known to be strongly invasive; hyphal mutants of SC5314: HLC52 (efg1/efg1), HLC54 (cph1/cph1 efg1/efg1) and JKC19 (cph1/cph1); Sap 1-3 and Sap 4-6 mutants of SC5314. Sonicated yeast cell and 10 x concentrated growth media fractions were used. E-cadherin was isolated from human oral epithelial cell membranes by immunoprecipitation using specific E-cadherin antibody and the degradation was detected by fluorography. Results: Proteinases associated with sonicated cell hyphal forms of SC5314 and JKC-19, and growth media of blastospore formed HLC-52, HLC-54, 32723 and B1134 were able to degrade E-cadherin. This degradation was more pronounced at pH 4. Hyphal forms expressing the transcription factor Efg1 seems to be important for the degradative ability. Conclusions: It seems possible that C. albicans clinical strains are able to degrade mucosal epithelial adhesion protein E-cadherin. The degradation may cause loss of integrity of the epithelium and aid the invasion of Candida between epithelial cells into deeper tissue. Aknowledgement: Supported by the Helsinki University Central Hospital EVO-grant (T1020Y0003).