title: Rapid control of wound infections by targeted photodynamic therapy monitored by in vivo bioluminescence imaging.
abstract: The worldwide rise in antibiotic resistance necessitates the development of novel antimicrobial strategies. In this study we report on the first use of a photochemical approach to destroy bacteria infecting a wound in an animal model. Following topical application, a targeted polycationic photosensitizer conjugate between poly-L-lysine and chlorin(e6) penetrated the gram (-) outer bacterial membrane, and subsequent activation with 660 nm laser light rapidly killed Escherichia coli infecting excisional wounds in mice. To facilitate real-time monitoring of infection, we used bacteria that expressed the lux operon from Photorhabdus luminescens; these cells emitted a bioluminescent signal that allowed the infection to be rapidly quantified, using a low-light imaging system. There was a light-dose dependent loss of luminescence in the wound treated with conjugate and light, not seen in untreated wounds. Treated wounds healed as well as control wounds, showing that the photodynamic treatment did not damage the host tissue. Our study points to the possible use of this methodology in the rapid control of wounds and other localized infections.
authors.affiliation: Wellman Laboratories of Photomedicine, Massachusetts General Hospital, Boston 02114-2698, USA. hamblin@helix.mgh.harvard.edu
authors.forename: Michael R
authors.initials: MR
authors.lastname: Hamblin
authors.forename: David A
authors.initials: DA
authors.lastname: O'Donnell
authors.forename: Naveen
authors.initials: N
authors.lastname: Murthy
authors.forename: Christopher H
authors.initials: CH
authors.lastname: Contag
authors.forename: Tayyaba
authors.initials: T
authors.lastname: Hasan
mesh_terms: D000818:Animals; D002735:Chlorophyllides; D004927:Escherichia coli Infections / Q000188:drug therapy; D049449:Luminescence; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D018462:Photobiology; D010778:Photochemotherapy; D011107:Polylysine / Q000627:therapeutic use; D011166:Porphyrins / Q000627:therapeutic use; D014946:Wound Infection / Q000188:drug therapy*
chemical_list: D002735:Chlorophyllides; D011166:Porphyrins; D011107:Polylysine; C062985:phytochlorin