Candida-associated denture stomatitis has a high rate of recurrence. Candida 
biofilms formed on denture acrylic are more resistant to antifungals than 
planktonic yeasts. Histatins, a family of basic peptides secreted by the major 
salivary glands in humans, especially histatin 5, possess significant antifungal 
properties. We examined antifungal activities of histatin 5 against planktonic 
or biofilm Candida albicans and Candida glabrata. Candida biofilms were 
developed on poly(methyl methacrylate) discs and treated with histatin 5 
(0.01-100 microM) or fluconazole (1-200 microM). The metabolic activity of the 
biofilms was measured by the XTT reduction assay. The fungicidal activity of 
histatin 5 against planktonic Candida was tested by microdilution plate assay. 
Biofilm and planktonic C. albicans GDH18, UTR-14 and 6122/06 were highly 
susceptible to histatin 5, with 50% RMA (concentration of the agent causing 50% 
reduction in the metabolic activity; biofilm) of 4.6 +/- 2.2, 6.9 +/- 3.7 and 
1.7 +/- 1.5 microM, and IC(50) (planktonic cells) of 3.0 +/- 0.5, 2.6 +/- 0.1 
and 4.8 +/- 0.5, respectively. Biofilms of C. glabrata GDH1407 and 6115/06 were 
less susceptible to histatin 5, with 50% RMA of 31.2 +/- 4.8 and 62.5 +/- 0.7 
microM, respectively. Planktonic C. glabrata was insensitive to histatin 5 
(IC(50) > 100 microM). Biofilm-associated Candida was highly resistant to 
fluconazole in the range 1-200 microM; e.g. at 100 microM only approximately 20% 
inhibition was observed for C. albicans, and approximately 30% inhibition for C. 
glabrata. These results indicate that histatin 5 exhibits antifungal activity 
against biofilms of C. albicans and C. glabrata developed on denture acrylic. C. 
glabrata is significantly less sensitive to histatin 5 than C. albicans.