Wellman Center for Photomedicine, Massachusetts General Hospital, Boston, MA, USA.
Photochem Photobiol. 2011 Mar-Apr;87(2):342-9. doi: 10.1111/j.1751-1097.2011.00886.x. Epub 2011 Feb 10.
Burn patients are at high risk of invasive fungal infections, which are a leading cause of morbidity, mortality, and related expense exacerbated by the emergence of drug resistant fungal strains. In this study, we investigated the use of UVC light (254 nm) for the treatment of yeast Candida albicans infection in mouse third degree burns. In vitro studies demonstrated that UVC could selectively kill the pathogenic C. albicans compared with a normal mouse keratinocyte cell line in a light exposure dependent manner. A mouse model of chronic C. albicans infection in non-lethal third degree burns was developed. The C. albicans strain was stably transformed with a version of the Gaussia princeps luciferase gene that allowed real-time bioluminescence imaging of the progression of C. albicans infection. UVC treatment with a single exposure carried out on day 0 (30 min postinfection) gave an average 2.16-log(10)-unit (99.2%) loss of fungal luminescence when 2.92 J cm(-2) UVC had been delivered, while UVC 24 h postinfection gave 1.94-log(10)-unit (95.8%) reduction of fungal luminescence after 6.48 J cm(-2). Statistical analysis demonstrated that UVC treatment carried out on both day 0 and day 1 significantly reduced the fungal bioburden of infected burns. UVC was found to be superior to a topical antifungal drug, nystatin cream. UVC was tested on normal mouse skin and no gross damage was observed 24 h after 6.48 J cm(-2). DNA lesions (cyclobutane pyrimidine dimers) were observed by immunofluorescence in normal mouse skin immediately after a 6.48 J cm(-2) UVC exposure, but the lesions were extensively repaired at 24 h after UVC exposure.
烧伤患者有发生侵袭性真菌感染的高风险,真菌感染是发病率、死亡率和相关费用增加的主要原因,而耐药真菌株的出现则使情况更加恶化。在这项研究中,我们研究了使用 UVC 光(254nm)治疗小鼠三度烧伤中的酵母白色念珠菌感染。体外研究表明,与正常小鼠角质形成细胞系相比,UVC 可以以光暴露依赖的方式选择性地杀死致病性白色念珠菌。建立了慢性白色念珠菌感染的非致死性三度烧伤小鼠模型。该白色念珠菌菌株被稳定转化为一种苍术发光酶基因的版本,该基因允许实时生物发光成像白色念珠菌感染的进展。在第 0 天(感染后 30 分钟)进行单次暴露的 UVC 治疗,当输送 2.92 J cm(-2) 的 UVC 时,真菌发光的平均损失为 2.16-log(10)-单位(99.2%),而 UVC 感染后 24 小时给予 6.48 J cm(-2) 时,真菌发光的减少为 1.94-log(10)-单位(95.8%)。统计分析表明,在第 0 天和第 1 天进行 UVC 治疗均可显著降低感染烧伤的真菌生物负荷。UVC 优于局部抗真菌药物制霉菌素乳膏。在正常小鼠皮肤中进行了 UVC 测试,在 6.48 J cm(-2) 后 24 小时未观察到明显的皮肤损伤。在接受 6.48 J cm(-2) 的 UVC 照射后立即通过免疫荧光观察到正常小鼠皮肤中的 DNA 损伤(环丁烷嘧啶二聚体),但在 UVC 照射后 24 小时,损伤得到了广泛修复。