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Antimicrobial Agents and Chemotherapy, January 2003, p. 70-76, Vol. 47, No. 1
0066-4804/03/$08.00+0     DOI: 10.1128/AAC.47.1.70-76.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Susceptibility of Candida dubliniensis to Salivary Histatin 3

Deirdre H. Fitzgerald,1 David C. Coleman,2 and Brian C. O'Connell1*

Department of Restorative Dentistry,1 Department of Oral Medicine and Pathology, School of Dental Science and Dublin Dental Hospital, Trinity College, University of Dublin, Dublin 2, Ireland2

Received 11 June 2002/ Returned for modification 30 July 2002/ Accepted 17 September 2002

Candida dubliniensis is a recently described Candida species associated with oral candidiasis in human immunodeficiency virus (HIV)-infected patients and patients with AIDS. The majority of C. dubliniensis clinical isolates tested to date are susceptible to the commonly used antifungal drugs, including fluconazole, ketoconazole, itraconazole, and amphotericin B. However, the appearance of fluconazole-resistant C. dubliniensis strains in this patient group is increasing. Histatins are a family of basic histidine-rich proteins present in human saliva which have therapeutic potential in the treatment of oral candidiasis. The mechanism of action of histatin is distinct from that of commonly used azole and polyene drugs. Characterization of the antifungal activity of histatin has mainly been carried out using C. albicans but it is also effective in killing C. glabrata and C. krusei. Here we report that C. dubliniensis is also susceptible to killing by histatin 3. The concentration of histatin 3 giving 50% killing (the IC50 value) ranged from 0.043 to 0.196 mg/ml among different strains of C. dubliniensis. The least-susceptible C. dubliniensis strain, P9224, was found to internalize histatin at a lower rate than the C. albicans reference strain CA132A. The dissociation constant (Kd) for the least-susceptible strain (C. dubliniensis 9224) was ninefold higher than that for the C. albicans reference strain. These results suggest that histatin 3 may have potential as an effective antifungal agent, particularly in the treatment of oral candidiasis in HIV-infected patients and patients with AIDS in which resistance to the commonly used antifungal drug fluconazole has emerged.

* Corresponding author. Mailing address: School of Dental Science, Trinity College, Lincoln Place, Dublin 2, Ireland. Phone: 353 1 612 7312. Fax: 353 1 612 7297. E-mail: boconne{at}dental.tcd.ie.

Antimicrobial Agents and Chemotherapy, January 2003, p. 70-76, Vol. 47, No. 1
0066-4804/03/$08.00+0     DOI: 10.1128/AAC.47.1.70-76.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.





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