Function of Candida albicansAdhesin Hwp1 in Biofilm Formation

ABSTRACTHwp1 is a well-characterized Candida albicanscell surface protein, expressed only on hyphae, that mediates tight binding to oral epithelial cells. Prior studies indicate that HWP1expression is dependent upon Bcr1, a key regulator of biofilm formation. Here we test the hypothesis that Hwp1 is required for biofilm formation. In an in vitro model, the hwp1/hwp1mutant produces a thin biofilm that lacks much of the hyphal mass found in the hwp1/HWP1reconstituted strain. In a biofilm cell retention assay, we find that the hwp1/hwp1mutant is defective in retention of nonadherent bcr1/bcr1mutant cells. In an in vivo rat venous catheter model, the hwp1/hwp1mutant has a severe biofilm defect, yielding only yeast microcolonies in the catheter lumen. These properties of the hwp1/hwp1mutant are consistent with its role as a hypha-specific adhesin and indicate that it is required for normal biofilm formation. Overexpression of HWP1in a bcr1/bcr1mutant background improves adherence in the in vivo catheter model. This finding provides additional support for the model that Hwp1 is critical for biofilm adhesion. Hwp1 is the first cell surface protein known to be required for C. albicansbiofilm formation in vivo and is thus an excellent therapeutic target.