Photodynamic therapy of oral Candida infection in a mouse model

Fernanda Freire; Cleber Ferraresi; Antonio Olavo C Jorge; Michael R Hamblin

doi:10.1016/j.jphotobiol.2016.03.049

Photodynamic therapy of oral Candida infection in a mouse model

J Photochem Photobiol B. 2016 Jun:159:161-8. doi: 10.1016/j.jphotobiol.2016.03.049. Epub 2016 Apr 1.

Authors

Fernanda Freire¹, Cleber Ferraresi², Antonio Olavo C Jorge³, Michael R Hamblin⁴

Affiliations

¹ Wellman Center for Photomedicine, Massachusetts General Hospital, Boston, MA, USA; Department of Biosciences and Oral Diagnosis, Institute of Science and Technology, Universidade Estadual Paulista (UNESP), São José dos Campos, São Paulo, Brazil.
² Wellman Center for Photomedicine, Massachusetts General Hospital, Boston, MA, USA.
³ Department of Biosciences and Oral Diagnosis, Institute of Science and Technology, Universidade Estadual Paulista (UNESP), São José dos Campos, São Paulo, Brazil.
⁴ Wellman Center for Photomedicine, Massachusetts General Hospital, Boston, MA, USA; Department of Dermatology, Harvard Medical School, Boston, MA, USA; Harvard-MIT Division of Health Sciences and Technology, Cambridge, MA, USA. Electronic address: hamblin@helix.mgh.harvard.edu.

Abstract

Species of the fungal genus Candida, can cause oral candidiasis especially in immunosuppressed patients. Many studies have investigated the use of photodynamic therapy (PDT) to kill fungi in vitro, but this approach has seldom been reported in animal models of infection. This study investigated the effects of PDT on Candida albicans as biofilms grown in vitro and also in an immunosuppressed mouse model of oral candidiasis infection. We used a luciferase-expressing strain that allowed non-invasive monitoring of the infection by bioluminescence imaging. The phenothiazinium salts, methylene blue (MB) and new methylene blue (NMB) were used as photosensitizers (PS), combined or not with potassium iodide (KI), and red laser (660nm) at four different light doses (10J, 20J, 40J and 60J). The best in vitro log reduction of CFU/ml on biofilm grown cells was: MB plus KI with 40J (2.31 log; p<0.001); and NMB without KI with 60J (1.77 log; p<0.001). These conditions were chosen for treating the in vivo model of oral Candida infection. After 5days of treatment the disease was practically eradicated, especially using MB plus KI with 40J. This study suggests that KI can potentiate PDT of fungal infection using MB (but not NMB) and could be a promising new approach for the treatment of oral candidiasis.

Keywords: Biofilm; Bioluminescence imaging; Candida albicans; Luciferase; Oral candidiasis; Photodynamic therapy.

MeSH terms

Animals
Candidiasis, Oral / drug therapy*
Disease Models, Animal*
Male
Mice
Mice, Inbred BALB C
Photochemotherapy*
Photosensitizing Agents / therapeutic use*

Substances

Photosensitizing Agents

Grants and funding

R01 AI050875/AI/NIAID NIH HHS/United States