Blue Light Rescues Mice from Potentially Fatal Pseudomonas aeruginosa Burn Infection: Efficacy, Safety, and Mechanism of Action

被引:172
作者
Dai, Tianhong [1 ,2 ]
Gupta, Asheesh [1 ,2 ,3 ,5 ]
Huang, Ying-Ying [1 ,2 ,4 ]
Yin, Rui [1 ,2 ]
Murray, Clinton K. [6 ]
Vrahas, Mark S. [7 ]
Sherwood, Margaret E. [1 ]
Tegos, George P. [1 ,2 ,8 ]
Hamblin, Michael R. [1 ,2 ,9 ]
机构
[1] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA
[2] Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA
[3] Def Inst Physiol & Allied Sci, Delhi, India
[4] Guangxi Med Univ, Dept Pathol, Nanning, Guangxi, Peoples R China
[5] Third Mil Med Univ, Southwest Hosp, Dept Dermatol, Chongqing, Peoples R China
[6] Brooke Army Med Ctr, Infect Dis Serv, Ft Sam Houston, TX 78234 USA
[7] Massachusetts Gen Hosp, Dept Orthopaed Surg, Boston, MA 02114 USA
[8] Univ New Mexico, Sch Med, Dept Pathol, Albuquerque, NM 87131 USA
[9] MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA
关键词
IN-VITRO; PHOTODYNAMIC THERAPY; ULTRAVIOLET-LIGHT; INACTIVATION; BACTERIA; PROPHYLAXIS; PORPHYRINS; RESISTANCE; MODEL; ACNE;
D O I
10.1128/AAC.01652-12
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
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 the treatment of acute, potentially lethal Pseudomonas aeruginosa burn infections in mice. Our in vitro studies demonstrated that the inactivation rate of P. aeruginosa cells by blue light was approximately 35-fold higher 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 and/or 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 an area-under-the-bioluminescence-time-curve (AUBC) analysis showed that a single exposure of blue light at 55.8 J/cm(2), applied 30 min after bacterial inoculation to the infected mouse burns, reduced the AUBC by approximately 100-fold in comparison with untreated and infected mouse burns (P < 0.0001). Histological analyses and terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling (TUNEL) assays indicated no significant damage in the mouse skin exposed to blue light at the effective antimicrobial dose. Survival analyses revealed that blue light increased the survival rate of the infected mice from 18.2% to 100% (P < 0.0001). In conclusion, blue light therapy might offer an effective and safe alternative to conventional antimicrobial therapy for P. aeruginosa burn infections.
引用
收藏
页码:1238 / 1245
页数:8
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