We have developed several mouse models of infections using pathogenic bacteria transfected with the gene complex coding for luciferase and its substrates and a sensitive photon-counting camera to image the light emitted from the animals in real time in order to follow the progress of the infection. These now comprise: excisional wounds, soft tissue infections in neutropenic and immunocompetent mice, chronic abscesses, burns, bladder infections, surgical site infections and nail infections.
Topical or interstitial administration of photosensitizers followed by illumination eradicates the infection, and in the case of pathogenic strains, save the lives of the mice which would otherwise die of systemic sepsis. The treatment does not damage host tissue, as demonstrated by the fact that the wound healing response is as good as or better than control wounds treated by alternative antimicrobial therapies. PDT may be applied to many stubborn clinical infections not easily treated with antibiotics.
Collaborative studies have shown that endodontic infections in humans also respond well to PDT.
Recently we have started to create and characterize animal models of localized fungal infections. These are based on eukaryotic cells that have been genetically engineered to express firefly and Gaussia luciferases together with topical application of substrate. These can also be treated with PDT.
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Garcez AS, Nunez SC, Hamblin MR, Suzuki H, Ribeiro MS. Photodynamic therapy associated with conventional endodontic treatment in patients with antibiotic resistant microflora. A Preliminary report. J Endodont, 2010; 36(9): 1463-1466
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Wainwright M, Dai T, Hamblin MR. Antimicrobial photodynamic therapy in the colon: delivering a light punch to the guts? Photochem Photobiol, 2011, 87(4):754-6.
Tanaka M, Kinoshita M, Yoshihara Y, Shinomiya N, Seki S, Nemoto N, Hamblin MR, Morimoto Y. Photodynamic therapy using intra-articular Photofrin for murine MRSA arthritis: biphasic light dose response for neutrophil-mediated antibacterial effect. Laser Surg Med, 2011, 43:221–229
Dai T, Bil de Arce VJ, Tegos GP, Hamblin MR, Blue dye and red light: a dynamic combination for prophylaxis and treatment of cutaneous Candida albicans infections in mice. Antimicrob Agents Chemother, 2011, 55(12): 5710–5717.
Sharma SK, Dai T, Kharkwal GB, Huang YY, Huang L, De Arce VJ, Tegos GP, Hamblin MR. Drug discovery of antimicrobial photosensitizers using animal models. Curr Pharm Des. 2011;17(13):1303-19.
Tanaka T, Mroz P, Dai T, Huang L, Morimoto Y, Kinoshita M, Yoshihara Y, Nemoto K, Shinomiya N, Seki S and Hamblin MR. Photodynamic therapy can induce a protective innate immune response against murine bacterial arthritis via neutrophil accumulation. PLoS ONE, 2012, 2012;7(6):e39823.
Huang YY, Tanaka M, Vecchio D, Garcia-Diaz M, Chang J, Morimoto Y, Hamblin MR. Photodynamic therapy induces an immune response against a bacterial pathogen. Expert Rev Clin Immunol. 2012 Jul;8(5):479-94
Vecchio D, Dai T, Huang L, Fantetti L, Roncucci G, Hamblin MR. Antimicrobial photodynamic therapy with RLP068 kills methicillin-resistant Staphylococcus aureus and improves wound healing in a mouse model of infected skin abrasion. J Biophotonics. 2012.