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Proceedings Paper

Targeted photodynamic therapy of established soft-tissue infections in mice
Author(s): Faten Gad; Touqir Zahra; Tayyaba Hasan; Michael R. Hamblin
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Paper Abstract

The worldwide rise in antibiotic resistance necessitates the development of novel antimicrobial strategies. Although many workers have used photodynamic therapy (PDT) to kill bacteria in vitro, the use of this approach has seldom been reported in vivo in animal models of infection. We have previously described the first use of PDT to treat excisional wound infections by Gram-negative bacteria in living mice. However these infected wound models used a short time after infection (30 min) before PDT. We now report on the use of PDT to treat an established soft-tissue infection in mice. We used Staphylococcus aureus stably transformed with a Photorhabdus luminescens lux operon (luxABCDE) that was genetically modified to be functional in Gram-positive bacteria. These engineered bacteria emitted bioluminescence allowing the progress of the infection to be monitored in both space and time with a lowlight imaging charged couple device (CCD) camera. One million cells were injected into one or both thigh muscles of mice that had previously been rendered neutropenic by cyclophosphamide administration. Twenty-four hours later the bacteria had multiplied more than one hundred-fold, and poly-L-lysine chlorin(e6) conjugate or free chlorin(e6) was injected into one area of infected muscle and imaged with the CCD camera. Thirty-minutes later red light from a diode laser was delivered as a surface spot or by interstitial fiber into the infection. There was a lightdose dependent loss of bioluminescence (to < 5% of that seen in control infections) not seen in untreated or light alone treated infections, but in some cases the infection recurred. Conjugate alone led to a lesser reduction in bioluminescence. Infections treated with free chlorin(e6) responded less and the infection subsequently increased over the succeeding days, probably due to PDT-mediated tissue damage. PDT-treated infected legs healed better than legs with untreated infections. This data shows that PDT may have applications in drug-resistant soft-tissue infections.

Paper Details

Date Published: 14 June 2004
PDF: 11 pages
Proc. SPIE 5315, Optical Methods for Tumor Treatment and Detection: Mechanisms and Techniques in Photodynamic Therapy XIII, (14 June 2004); doi: 10.1117/12.528390
Show Author Affiliations
Faten Gad, Massachusetts General Hospital (United States)
Harvard Medical School (United States)
Touqir Zahra, Massachusetts General Hospital (United States)
Harvard Medical School (United States)
Tayyaba Hasan, Massachusetts General Hospital (United States)
Harvard Medical School (United States)
Michael R. Hamblin, Massachusetts General Hospital (United States)
Harvard Medical School (United States)


Published in SPIE Proceedings Vol. 5315:
Optical Methods for Tumor Treatment and Detection: Mechanisms and Techniques in Photodynamic Therapy XIII
David Kessel, Editor(s)

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