Optical monitoring and treatment of potentially lethal wound infections in vivo.
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.
Wellman Laboratories of Photomedicine, Massachusetts General Hospital, and Department of Dermatology, Harvard Medical School, Boston, Massachusetts 02114, USA. hamblin@helix.mgh.harvard.edu
Michael R
MR
Hamblin
Touqir
T
Zahra
Christopher H
CH
Contag
Albert T
AT
McManus
Tayyaba
T
Hasan
D000818:Animals; D004307:Dose-Response Relationship, Radiation; D008027:Light; D008163:Luminescent Measurements; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010778:Photochemotherapy; D011107:Polylysine / Q000031:analogs & derivatives / Q000627:therapeutic use; D011552:Pseudomonas Infections / Q000150:complications / Q000188:drug therapy*; D011550:Pseudomonas aeruginosa / Q000187:drug effects / Q000528:radiation effects; D012867:Skin / Q000293:injuries / Q000473:pathology; D013997:Time Factors; D014945:Wound Healing / Q000187:drug effects; D014946:Wound Infection / Q000150:complications / Q000188:drug therapy*
D011107:Polylysine