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Antimicrobial Agents and Chemotherapy, June 2004, p. 2000-2006, Vol. 48, No. 6
0066-4804/04/$08.00+0     DOI: 10.1128/AAC.48.6.2000-2006.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Susceptibility of Candida Species to Photodynamic Effects of Photofrin

Joseph M. Bliss,1,{dagger} Chad E. Bigelow,2 Thomas H. Foster,2,3 and Constantine G. Haidaris4,5*

Department of Pediatrics,1 Department of Radiology,3 Department of Microbiology and Immunology,4 Center for Oral Biology, University of Rochester School of Medicine and Dentistry, Rochester, New York 14642,5 Institute of Optics, University of Rochester, Rochester, New York 146272

Received 11 September 2003/ Returned for modification 20 January 2004/ Accepted 10 February 2004

The in vitro susceptibility of pathogenic Candida species to the photodynamic effects of the clinically approved photosensitizing agent Photofrin was examined. Internalization of Photofrin by Candida was confirmed by confocal fluorescence microscopy, and the degree of uptake was dependent on incubation concentration. Uptake of Photofrin by Candida and subsequent sensitivity to irradiation was influenced by culture conditions. Photofrin uptake was poor in C. albicans blastoconidia grown in nutrient broth. However, conversion of blastoconidia to filamentous forms by incubation in defined tissue culture medium resulted in substantial Photofrin uptake. Under conditions where Photofrin was effectively taken up by Candida, irradiated organisms were damaged in a drug dose- and light-dependent manner. Uptake of Photofrin was not inhibited by azide, indicating that the mechanism of uptake was not dependent on energy provided via electron transport. Fungal damage induced by Photofrin-mediated photodynamic therapy (PDT) was determined by evaluation of metabolic activity after irradiation. A strain of C. glabrata took up Photofrin poorly and was resistant to killing after irradiation. In contrast, two different strains of C. albicans displayed comparable levels of sensitivity to PDT. Furthermore, a reference strain of C. krusei that is relatively resistant to fluconazole compared to C. albicans was equally sensitive to C. albicans at Photofrin concentrations of >=3 µg/ml. The results indicate that photodynamic therapy may be a useful adjunct or alternative to current anti-Candida therapeutic modalities, particularly for superficial infections on surfaces amenable to illumination.

* Corresponding author. Mailing address: University of Rochester School of Medicine and Dentistry, 601 Elmwood Ave., Box 672, Rochester, NY 14642. Phone: (585) 275-0678. Fax: (585) 473-9573. E-mail: haid{at}mail.rochester.edu.

{dagger} Present address: Women and Infants' Hospital of Rhode Island, Brown Medical School, Providence, RI 02905.

Antimicrobial Agents and Chemotherapy, June 2004, p. 2000-2006, Vol. 48, No. 6
0066-4804/04/$08.00+0     DOI: 10.1128/AAC.48.6.2000-2006.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



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