Optical Monitoring and Treatment of Potentially Lethal Wound Infections In Vivo

• Published in: The Journal of infectious diseases Vol. 187; no. 11; pp. 1717 - 1726
• Main Authors: Hamblin, Michael R., Zahra, Touqir, Contag, Christopher H., McManus, Albert T., Hasan, Tayyaba
• Format: Journal Article
• Language: English
• Published: Chicago, IL The University of Chicago Press 01-06-2003; University of Chicago Press; Oxford University Press
• Subjects: Animals; Antibiotics. Antiinfectious agents. Antiparasitic agents; Bacteria; Bacterial diseases; Biological and medical sciences; Dose-Response Relationship, Radiation; Experimental bacterial diseases and models; Imaging; Infections; Infectious diseases; Light; Luminescence; Luminescent Measurements; Male; Medical sciences; Mice; Mice, Inbred BALB C; Miscellaneous. Antibiotics with multiple activities; Pharmacology. Drug treatments; Photochemotherapy; Polylysine - analogs & derivatives; Polylysine - therapeutic use; Pseudomonas aeruginosa; Pseudomonas aeruginosa - drug effects; Pseudomonas aeruginosa - radiation effects; Pseudomonas Infections - complications; Pseudomonas Infections - drug therapy; Skin - injuries; Skin - pathology; Time Factors; Virulence factors; Wound healing; Wound Healing - drug effects; Wound Infection - complications; Wound Infection - drug therapy; Wound infections; Animal model; Bioluminescence; Photodynamic therapy; Rodentia; Wound; In vivo; Vertebrata; Image analysis; Mammalia; Treatment; Mouse; Surveillance; Bacteria; Micrococcales; Micrococcaceae; Staphylococcus aureus
• ISSN: 0022-1899; 1537-6613
• DOI: 10.1086/375244

We report on the use of optical techniques to monitor and treat Pseudomonas aeruginosa wound infections in mice. Bioluminescent bacteria transduced with a plasmid containing a bacterial lux gene operon allow the infection in excisional mouse wounds to be imaged by use of a sensitive charge-coupled device camera. Photodynamic therapy (PDT) targeted bacteria, by use of a polycationic photosensitizer conjugate, which is designed to penetrate the gram-negative cell wall and was topically applied to the wound and was followed by red-light illumination. There was a rapid light dose-dependent loss of luminescence, as measured by image analysis, in the wounds treated with conjugate and light, a loss that was not seen in untreated wounds, wounds treated with light alone, or wounds treated with conjugate alone. P. aeruginosa was invasive in our mouse model, and all 3 groups of control mice died within 5 days; in contrast, 90% of PDT-treated mice survived. PDT-treated wounds healed significantly faster than did silver nitrate-treated wounds, and this was not due to either inhibition of healing by silver nitrate or stimulation of healing by PDT