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

Abstract

ABSTRACTBlue 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 lethalPseudomonas aeruginosaburn infections in mice. Ourin vitrostudies demonstrated that the inactivation rate ofP. aeruginosacells by blue light was approximately 35-fold higher than that of keratinocytes (P= 0.0014). Transmission electron microscopy revealed blue light-mediated intracellular damage toP. aeruginosacells. Fluorescence spectroscopy suggested that coproporphyrin III and/or uroporphyrin III are possibly the intracellular photosensitive chromophores associated with the blue light inactivation ofP. aeruginosa.In vivostudies using anin vivobioluminescence imaging technique and an area-under-the-bioluminescence-time-curve (AUBC) analysis showed that a single exposure of blue light at 55.8 J/cm2, 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 forP. aeruginosaburn infections.