title: Antimicrobial blue light inactivation of Candida albicans: In vitro and in vivo studies.
abstract: Fungal infections are a common cause of morbidity, mortality and cost in critical care populations. The increasing emergence of antimicrobial resistance necessitates the development of new therapeutic approaches for fungal infections. In the present study, we investigated the effectiveness of an innovative approach, antimicrobial blue light (aBL), for inactivation of Candida albicans in vitro and in infected mouse burns. A bioluminescent strain of C. albicans was used. The susceptibilities to aBL (415 nm) were compared between C. albicans and human keratinocytes. The potential development of aBL resistance by C. albicans was investigated via 10 serial passages of C. albicans on aBL exposure. For the animal study, a mouse model of thermal burn infected with the bioluminescent C. albicans strain was used. aBL was delivered to mouse burns approximately 12 h after fungal inoculation. Bioluminescence imaging was performed to monitor in real time the extent of infection in mice. The results obtained from the studies demonstrated that C. albicans was approximately 42-fold more susceptible to aBL than human keratinocytes. Serial passaging of C. albicans on aBL exposure implied a tendency of reduced aBL susceptibility of C. albicans with increasing numbers of passages; however, no statistically significant difference was observed in the post-aBL survival rate of C. albicans between the first and the last passage (P>0.05). A single exposure of 432 J/cm(2) aBL reduced the fungal burden in infected mouse burns by 1.75-log10 (P=0.015). Taken together, our findings suggest aBL is a potential therapeutic for C. albicans infections.
authors.affiliation: a Department of Plastic Surgery and Cosmetic , The Second People's Hospital of Guangdong Province , Guangzhou , China.|b Wellman Center for Photomedicine, Massachusetts General Hospital , Boston , MA , USA.|c Department of Dermatology , Harvard Medical School , Boston , MA , USA.
authors.forename: Yunsong
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: b Wellman Center for Photomedicine, Massachusetts General Hospital , Boston , MA , USA.|d School of Medicine, Tongji University , Shanghai , China.
authors.forename: Yingbo
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: b Wellman Center for Photomedicine, Massachusetts General Hospital , Boston , MA , USA.|c Department of Dermatology , Harvard Medical School , Boston , MA , USA.|e Shanghai Dermatology Hospital , Shanghai , China.
authors.forename: Jia
authors.initials: J
authors.lastname: Chen
authors.affiliation: b Wellman Center for Photomedicine, Massachusetts General Hospital , Boston , MA , USA.|c Department of Dermatology , Harvard Medical School , Boston , MA , USA.|f Department of Laser Medicine , Chinese PLA General Hospital , Beijing , China.
authors.forename: Yucheng
authors.initials: Y
authors.lastname: Wang
authors.affiliation: b Wellman Center for Photomedicine, Massachusetts General Hospital , Boston , MA , USA.
authors.forename: Margaret E
authors.initials: ME
authors.lastname: Sherwood
authors.affiliation: g Infectious Disease Service, Brooke Army Medical Center, Fort Sam Houston , TX , USA.
authors.forename: Clinton K
authors.initials: CK
authors.lastname: Murray
authors.affiliation: h Department of orthopedic Surgery , Massachusetts General Hospital, Harvard Medical School , Boston , MA , USA.
authors.forename: Mark S
authors.initials: MS
authors.lastname: Vrahas
authors.affiliation: i Division of Infectious Diseases, Massachusetts General Hospital, Harvard Medical School , Boston , MA , USA.
authors.forename: David C
authors.initials: DC
authors.lastname: Hooper
authors.affiliation: b Wellman Center for Photomedicine, Massachusetts General Hospital , Boston , MA , USA.|c Department of Dermatology , Harvard Medical School , Boston , MA , USA.|j Harvard-MIT Division of Health Sciences and Technology , Cambridge , MA , USA.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Hamblin
authors.affiliation: b Wellman Center for Photomedicine, Massachusetts General Hospital , Boston , MA , USA.|c Department of Dermatology , Harvard Medical School , Boston , MA , USA.
authors.forename: Tianhong
authors.initials: T
authors.lastname: Dai
mesh_terms: D000818:Animals; D002056:Burns / Q000382:microbiology*; D002176:Candida albicans / Q000378:metabolism / Q000528:radiation effects* / Q000648:ultrastructure; D002177:Candidiasis / Q000382:microbiology / Q000628:therapy*; D004195:Disease Models, Animal; D006801:Humans; D015603:Keratinocytes / Q000382:microbiology / Q000528:radiation effects*; D008027:Light; D008163:Luminescent Measurements; D051379:Mice; D046529:Microscopy, Electron, Transmission; D012692:Serial Passage; D014946:Wound Infection / Q000382:microbiology / Q000628:therapy*
keywords: antimicrobial blue light; bioluminescence imagining; burn; candida albicans; endogenous photosensitizer; mouse model