Hamblin Michael R, Zahra Touqir, Contag Christopher H, McManus Albert T, Hasan Tayyaba
Wellman Laboratories of Photomedicine, Massachusetts General Hospital, and Department of Dermatology, Harvard Medical School, Boston, Massachusetts 02114, USA.
J Infect Dis. 2003 Jun 1;187(11):1717-25. doi: 10.1086/375244. Epub 2003 May 15.
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.
我们报告了利用光学技术监测和治疗小鼠铜绿假单胞菌伤口感染的情况。用含有细菌荧光素酶基因操纵子的质粒转导的生物发光细菌,使得切除的小鼠伤口感染情况可通过使用灵敏的电荷耦合器件相机进行成像。通过使用一种聚阳离子光敏剂共轭物对细菌进行光动力疗法(PDT),该共轭物旨在穿透革兰氏阴性菌细胞壁,将其局部应用于伤口,随后进行红光照射。通过图像分析测量,在用共轭物和光处理的伤口中,出现了与光剂量相关的快速发光损失,而在未处理的伤口、仅用光处理的伤口或仅用共轭物处理的伤口中未观察到这种损失。铜绿假单胞菌在我们的小鼠模型中具有侵袭性,所有3组对照小鼠在5天内死亡;相比之下,90%接受PDT治疗的小鼠存活了下来。接受PDT治疗的伤口愈合速度明显快于硝酸银治疗的伤口,这既不是由于硝酸银抑制愈合,也不是由于PDT刺激愈合。