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Antimicrob Agents Chemother. Blue light rescues mice from potentially fatal Pseudomonas aeruginosa burn infection: efficacy, safety, and mechanism of action
[Source: Antimicrobial Agents and Chemotherapy, full page: (LINK). Abstract, edited.]
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Blue light rescues mice from potentially fatal Pseudomonas aeruginosa burn infection: efficacy, safety, and mechanism of action
Tianhong Dai 1,2, Asheesh Gupta 1,2,3, Ying-Ying Huang 1,2,4, Rui Yin 1,2,5, Clinton K. Murray 6, Mark S. Vrahas 7, Margaret Sherwood 1, George P Tegos 1,2,8 and Michael R. Hamblin 1,2,9,*
Author Affiliations: <SUP>1</SUP>Wellman Center for Photomedicine, Massachusetts General Hospital, Boston, MA; <SUP>2</SUP>Department of Dermatology, Harvard Medical School, Boston, MA; <SUP>3</SUP>Defence Institute of Physiology & Allied Sciences, Delhi 110 054, India; <SUP>4</SUP>Department of Pathology, Guangxi Medical University, Nanning, Guangxi, China; <SUP>5</SUP>Department of Dermatology, Southwest Hospital, Third Military Medical University, Chongqing, China; <SUP>6</SUP>Infectious Disease Service, Brooke Army Medical Center, Fort Sam Houston, TX; <SUP>7</SUP>Department of Orthopedic Surgery, Massachusetts General Hospital, Boston, MA; <SUP>8</SUP>Department of Pathology, School of Medicine, University of New Mexico, Albuquerque, NM; <SUP>9</SUP>Harvard-MIT Division of Health Sciences and Technology, Cambridge, MA
ABSTRACT
Blue light has attracted increasing attention due to its intrinsic antimicrobial effect without the addition of exogenous photosensitizers. However, the use of blue light for wound infections has not been established yet. In this study, we demonstrated the efficacy of blue light at 415 nm for treatment of acute, potentially lethal Pseudomonas aeruginosa burn infections in mice. In vitro studies demonstrated that the inactivation rate of P. aeruginosa cells by blue light was approximately 35-fold faster than that of keratinocytes (P=0.0014). Transmission electron microscopy revealed blue light mediated intracellular damage to P. aeruginosa cells. Fluorescence spectroscopy suggested that coproporphyrin III or/and uroporphyrin III are possibly the intracellular photosensitive chromophores associated with the blue light inactivation of P. aeruginosa. In vivo studies using an in vivo bioluminescence imaging technique and the area-under-the-bioluminescence-time-curve (AUBC) analysis showed that a single exposure of blue light at 55.8 J/cm<SUP>2</SUP>, applied 30 min after bacterial inoculation to the infected mouse burns, reduced the AUBC by an approximately 100-fold in comparison with untreated and infected mouse burns (P<0.0001). Histological analysis and TUNEL assay indicated no significant damages in the mouse skin exposed to blue light at the effective antimicrobial dose. Survival analysis revealed that blue light increased the survival rate of infected mice from 18.2% to 100% (P<0.0001). In conclusion, blue light therapy may offer an effective and safe alternative to conventional antimicrobial therapy for P. aeruginosa burn infections.
FOOTNOTES
* Address correspondence to: Michael R. Hamblin, Ph.D., Associate Professor, Wellman Center for Photomedicine, Massachusetts General Hospital, 40 Blossom Street, Boston, MA 02114, Phone: 617-726-6182, Email: hamblin@helix.mgh.harvard.edu
Copyright ? 2012, American Society for Microbiology. All Rights Reserved.
-Tianhong Dai 1,2, Asheesh Gupta 1,2,3, Ying-Ying Huang 1,2,4, Rui Yin 1,2,5, Clinton K. Murray 6, Mark S. Vrahas 7, Margaret Sherwood 1, George P Tegos 1,2,8 and Michael R. Hamblin 1,2,9,*
Author Affiliations: <SUP>1</SUP>Wellman Center for Photomedicine, Massachusetts General Hospital, Boston, MA; <SUP>2</SUP>Department of Dermatology, Harvard Medical School, Boston, MA; <SUP>3</SUP>Defence Institute of Physiology & Allied Sciences, Delhi 110 054, India; <SUP>4</SUP>Department of Pathology, Guangxi Medical University, Nanning, Guangxi, China; <SUP>5</SUP>Department of Dermatology, Southwest Hospital, Third Military Medical University, Chongqing, China; <SUP>6</SUP>Infectious Disease Service, Brooke Army Medical Center, Fort Sam Houston, TX; <SUP>7</SUP>Department of Orthopedic Surgery, Massachusetts General Hospital, Boston, MA; <SUP>8</SUP>Department of Pathology, School of Medicine, University of New Mexico, Albuquerque, NM; <SUP>9</SUP>Harvard-MIT Division of Health Sciences and Technology, Cambridge, MA
ABSTRACT
Blue light has attracted increasing attention due to its intrinsic antimicrobial effect without the addition of exogenous photosensitizers. However, the use of blue light for wound infections has not been established yet. In this study, we demonstrated the efficacy of blue light at 415 nm for treatment of acute, potentially lethal Pseudomonas aeruginosa burn infections in mice. In vitro studies demonstrated that the inactivation rate of P. aeruginosa cells by blue light was approximately 35-fold faster than that of keratinocytes (P=0.0014). Transmission electron microscopy revealed blue light mediated intracellular damage to P. aeruginosa cells. Fluorescence spectroscopy suggested that coproporphyrin III or/and uroporphyrin III are possibly the intracellular photosensitive chromophores associated with the blue light inactivation of P. aeruginosa. In vivo studies using an in vivo bioluminescence imaging technique and the area-under-the-bioluminescence-time-curve (AUBC) analysis showed that a single exposure of blue light at 55.8 J/cm<SUP>2</SUP>, applied 30 min after bacterial inoculation to the infected mouse burns, reduced the AUBC by an approximately 100-fold in comparison with untreated and infected mouse burns (P<0.0001). Histological analysis and TUNEL assay indicated no significant damages in the mouse skin exposed to blue light at the effective antimicrobial dose. Survival analysis revealed that blue light increased the survival rate of infected mice from 18.2% to 100% (P<0.0001). In conclusion, blue light therapy may offer an effective and safe alternative to conventional antimicrobial therapy for P. aeruginosa burn infections.
FOOTNOTES
* Address correspondence to: Michael R. Hamblin, Ph.D., Associate Professor, Wellman Center for Photomedicine, Massachusetts General Hospital, 40 Blossom Street, Boston, MA 02114, Phone: 617-726-6182, Email: hamblin@helix.mgh.harvard.edu
Copyright ? 2012, American Society for Microbiology. All Rights Reserved.
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