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.

 

Related Publications
Hamblin MR, O’Donnell DA, Murthy N, Contag CH, Hasan T. Rapid control of wound infections by targeted photodynamic therapy monitored by in vivo bioluminescence imaging. Photochem Photobiol 2002;75(1):51-7

Hamblin MR, Zahra T, Contag CH, McManus AT, Hasan T. Optical monitoring and treatment of potentially lethal wound infections in vivo. J Infect Dis 2003;187(11):1717-25.

Gad F, Zahra T, Francis KP, Hasan T, Hamblin MR. Targeted photodynamic therapy of established soft-tissue infections in mice.  Photochem Photobiol Sci 2004; 3: 451-8

Hamblin MR, Hasan T.  Photodynamic therapy: a new antimicrobial approach to infectious disease?  Photochem Photobiol Sci 2004; 3(5): 436-50

Demidova TN, Gad F, Zahra T, Francis KP, Hamblin MR. Monitoring photodynamic therapy of localized infections by bioluminescence imaging of genetically engineered bacteria. J Photochem Photobiol B. 2005; 81:15-25

Lambrechts SA, Demidova TN, Aalders MC, Hasan T, Hamblin MR. Photodynamic therapy for Staphylococcus aureus infected burn wounds in mice. Photochem Photobiol Sci. 2005; 4: 503 - 509

Garcez, AS; Ribeiro MS, Tegos GP, Nunez SC, Jorge AO, Hamblin MR. Antimicrobial photodynamic therapy combined with conventional endodontic treatment to combat root canal infection. Lasers Surg Med. 2007 Jan;39(1): 59-66.

Garcez AS, Nunez SC, Lage-Marques JL, Hamblin MR, Ribeiro MS. Photonic real-time monitoring of bacterial reduction in root canals by genetically engineered bacteria after chemomechanical endodontic therapy. Braz Dent J. 2007;18(3):202-7.

Garcez, AS, Nunez SC, Hamblin MR, and Ribeiro MS. Antimicrobial effects of photodynamic therapy on patients with necrotic pulps and periapical lesion. J Endodont, 2008, 34:138-142

Dai T, Tegos GP, Lu Z, Huang L, Zhiyentayev T, Franklin MJ, Baer DG, Hamblin MR. Photodynamic therapy for Acinetobacter baumannii burn infections in mice. Antimicrob. Agents Chemother. 2009 53: 3929-3934.

Dai T, Huang Y-Y, Hamblin MR. Photodynamic therapy for localized infections – state of the art. Photodiagn Photodyn Ther. 2009, 6, 170-188.

Dai T, Tegos GP, Zhiyentayev  T,  Mylonakis E, Hamblin MR. Photodynamic Therapy for Methicillin-Resistant Staphylococcus aureus Infection in a Mouse Skin Abrasion Model. Lasers Surg Med; 2010, 42: 38–44

Ragas X, Dai T, Tegos GP, Agut M, Nonell S, Hamblin MR. Photodynamic inactivation of Acinetobacter baumannii using phenothiazinium dyes: in-vitro and in-vivo studies. Lasers Surg Med; 2010, 42:384–390.

Hamblin MR, Dai T. Can surgical site infections be treated by photodynamic therapy? Photodiagnosis PhotodynTher, 2010, 7(2): 134-136

Huang L; Dai T; Hamblin MR. Antimicrobial photodynamic inactivation and photodynamic therapy for infections. Methods Mol Biol. 2010, 635: 155-73.

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

Lu Z, Dai T, Huang L, Kurup DB, Tegos GP, Jahnke A, Wharton T, Hamblin, MR. Photodynamic therapy with a cationic functionalized fullerene rescues mice from fatal wound infections. Nanomedicine UK. 2010; 5(10):1525-33.

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.

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