Streptococcus oralis and Candida albicans Synergistically Activate [mu]-Calpain to Degrade E-cadherin From Oral Epithelial Junctions

Streptococcus oralis forms robust mucosal biofilms with Candida albicans that have increased pathogenic potential. In this study, using oral epithelial cultures, organotypic oral mucosal constructs, and a mouse model of oral infection, we demonstrated that S. oralis augmented C. albicans invasion th...

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Bibliographic Details
Published in:The Journal of infectious diseases 2016-09, Vol.214 (6), p.925-934
Main Authors: Xu, Hongbin, Sobue, Takanori, Bertolini, Martinna, Thompson, Angela, Dongari-Bagtzoglou, Anna
Format: Article
Language:English
Subjects:
Candida albicans
Streptococcus oralis
Online Access:Get full text
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Summary:Streptococcus oralis forms robust mucosal biofilms with Candida albicans that have increased pathogenic potential. In this study, using oral epithelial cultures, organotypic oral mucosal constructs, and a mouse model of oral infection, we demonstrated that S. oralis augmented C. albicans invasion through epithelial junctions. C. albicans and S. oralis decreased epithelial E-cadherin levels by synergistically increasing [mu]-calpain, a proteolytic enzyme that targets E-cadherin. In the mouse coinfection model this was accompanied by increased fungal kidney dissemination. Coinfection with a secreted aspartyl protease (sap) mutant sap2456 and S. oralis increased [mu]-calpain and triggered mucosal invasion and systemic dissemination, suggesting that fungal protease activity is not required for invasion during coinfection. We conclude that C. albicans and S. orali s synergize to activate host enzymes that cleave epithelial junction proteins and increase fungal invasion.
ISSN:0022-1899
1537-6613
DOI:10.1093/infdis/jiw201