Affiliation:
1. Department of Oral Biology, University at Buffalo, Buffalo, New York, USA
Abstract
ABSTRACT
Candida albicans
, a commensal fungus of the oral microbiome, causes oral candidiasis in humans with localized or systemic immune deficiencies. Secreted aspartic proteinases (Saps) are a family of 10 related proteases and are virulence factors due to their proteolytic activity, as well as their roles in adherence and colonization of host tissues. We found that mice infected sublingually with
C. albicans
cells overexpressing Sap6 (
SAP6
OE and a Δ
sap8
strain) had thicker fungal plaques and more severe oral infection, while infection with the Δ
sap6
strain was attenuated. These hypervirulent strains had highly aggregative colony structure
in vitro
and higher secreted proteinase activity; however, the levels of proteinase activity of
C. albicans
Saps did not uniformly match their abilities to damage cultured oral epithelial cells (SCC-15 cells). Hyphal induction in cells overexpressing Sap6 (
SAP6
OE and Δ
sap8
cells) resulted in formation of large cell-cell aggregates. These aggregates could be produced in germinated wild-type cells by addition of native or heat-inactivated Sap6. Sap6 bound only to germinated cells and increased
C. albicans
adhesion to oral epithelial cells. The adhesion properties of Sap6 were lost upon deletion of its integrin-binding motif (RGD) and could be inhibited by addition of RGD peptide or anti-integrin antibodies. Thus, Sap6 (but not Sap5) has an alternative novel function in cell-cell aggregation, independent of its proteinase activity, to promote infection and virulence in oral candidiasis.
Publisher
American Society for Microbiology
Subject
Infectious Diseases,Immunology,Microbiology,Parasitology