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Open Access Research article

Selective photoinactivation of Candida albicans in the non-vertebrate host infection model Galleria mellonella

José Chibebe Junior123, Caetano P Sabino45, Xiaojiang Tan26, Juliana C Junqueira1*, Yan Wang27, Beth B Fuchs2, Antonio OC Jorge1, George P Tegos489, Michael R Hamblin1049 and Eleftherios Mylonakis112

Author Affiliations

1 Department of Biosciences and Oral Diagnosis, Univ Estadual Paulista/UNESP, São José dos Campos, SP 12245000, Brazil

2 Division of Infectious Diseases, Massachusetts General Hospital, Boston, MA 02114, USA

3 Department of Restorative Dentistry, Faculty of Pindamonhangaba, Pindamonhangaba, SP 12422970, Brazil

4 Wellman Center for Photomedicine, Massachusetts General Hospital, Boston, MA 02114, USA

5 Center for Lasers and Applications, Nuclear and Energy Research Institute, São Paulo, SP 05508000, Brazil

6 Huiqiao Department, Nanfang Hospital, Southern Medical University, Guangzhou 510515, People’s Republic of China

7 School of Pharmacy, Second Military Medical University, Shanghai 200433, China

8 Department of Pathology and Center for Molecular Discovery, University of New Mexico, Albuquerque, NM 87131, USA

9 Department of Dermatology, Harvard Medical School, Boston, MA 02114, USA

10 Harvard-MIT Division of Health Sciences and Technology, Cambridge, MA 02139, USA

11 Warren Alpert Medical School, Brown University/Rhode Island and Miriam Hospitals, Providence, RI 02903, USA

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BMC Microbiology 2013, 13:217  doi:10.1186/1471-2180-13-217

Published: 1 October 2013

Abstract

Background

Candida spp. are recognized as a primary agent of severe fungal infection in immunocompromised patients, and are the fourth most common cause of bloodstream infections. Our study explores treatment with photodynamic therapy (PDT) as an innovative antimicrobial technology that employs a nontoxic dye, termed a photosensitizer (PS), followed by irradiation with harmless visible light. After photoactivation, the PS produces either singlet oxygen or other reactive oxygen species (ROS) that primarily react with the pathogen cell wall, promoting permeabilization of the membrane and cell death. The emergence of antifungal-resistant Candida strains has motivated the study of antimicrobial PDT (aPDT) as an alternative treatment of these infections. We employed the invertebrate wax moth Galleria mellonella as an in vivo model to study the effects of aPDT against C. albicans infection. The effects of aPDT combined with conventional antifungal drugs were also evaluated in G. mellonella.

Results

We verified that methylene blue-mediated aPDT prolonged the survival of C. albicans infected G. mellonella larvae. The fungal burden of G. mellonella hemolymph was reduced after aPDT in infected larvae. A fluconazole-resistant C. albicans strain was used to test the combination of aPDT and fluconazole. Administration of fluconazole either before or after exposing the larvae to aPDT significantly prolonged the survival of the larvae compared to either treatment alone.

Conclusions

G. mellonella is a useful in vivo model to evaluate aPDT as a treatment regimen for Candida infections. The data suggests that combined aPDT and antifungal therapy could be an alternative approach to antifungal-resistant Candida strains.

Keywords:
Candida albicans; Photodynamic therapy; Galleria mellonella