Dai Tianhong, Fuchs Beth B, Coleman Jeffrey J, Prates Renato A, Astrakas Christos, St Denis Tyler G, Ribeiro Martha S, Mylonakis Eleftherios, Hamblin Michael R, Tegos George P
Wellman Center for Photomedicine, Massachusetts General Hospital Boston, MA, USA.
Front Microbiol. 2012 Apr 10;3:120. doi: 10.3389/fmicb.2012.00120. eCollection 2012.
Opportunistic fungal pathogens may cause superficial or serious invasive infections, especially in immunocompromised and debilitated patients. Invasive mycoses represent an exponentially growing threat for human health due to a combination of slow diagnosis and the existence of relatively few classes of available and effective antifungal drugs. Therefore systemic fungal infections result in high attributable mortality. There is an urgent need to pursue and deploy novel and effective alternative antifungal countermeasures. Photodynamic therapy (PDT) was established as a successful modality for malignancies and age-related macular degeneration but photodynamic inactivation has only recently been intensively investigated as an alternative antimicrobial discovery and development platform. The concept of photodynamic inactivation requires microbial exposure to either exogenous or endogenous photosensitizer molecules, followed by visible light energy, typically wavelengths in the red/near infrared region that cause the excitation of the photosensitizers resulting in the production of singlet oxygen and other reactive oxygen species that react with intracellular components, and consequently produce cell inactivation and death. Antifungal PDT is an area of increasing interest, as research is advancing (i) to identify the photochemical and photophysical mechanisms involved in photoinactivation; (ii) to develop potent and clinically compatible photosensitizers; (iii) to understand how photoinactivation is affected by key microbial phenotypic elements multidrug resistance and efflux, virulence and pathogenesis determinants, and formation of biofilms; (iv) to explore novel photosensitizer delivery platforms; and (v) to identify photoinactivation applications beyond the clinical setting such as environmental disinfectants.
机会性真菌病原体可引起浅表或严重的侵袭性感染，尤其是在免疫功能低下和身体虚弱的患者中。侵袭性真菌病对人类健康构成的威胁呈指数级增长，这是由于诊断缓慢以及可用的有效抗真菌药物种类相对较少。因此，系统性真菌感染导致较高的归因死亡率。迫切需要寻求和采用新型有效的替代抗真菌对策。光动力疗法（PDT）已成为治疗恶性肿瘤和年龄相关性黄斑变性的成功方法，但光动力灭活作为一种替代抗菌发现和开发平台，直到最近才得到深入研究。光动力灭活的概念要求微生物暴露于外源性或内源性光敏剂分子，然后是可见光能量，通常是红色/近红外区域的波长，这会导致光敏剂激发，从而产生单线态氧和其他活性氧物质，这些物质与细胞内成分发生反应，进而导致细胞失活和死亡。抗真菌光动力疗法是一个越来越受关注的领域，因为研究正在推进以下方面：（i）确定光灭活所涉及的光化学和光物理机制；（ii）开发有效的且临床适用的光敏剂；（iii）了解光灭活如何受到关键微生物表型因素的影响，如多药耐药性和外排、毒力和发病机制决定因素以及生物膜的形成；（iv）探索新型光敏剂递送平台；以及（v）确定临床环境以外的光灭活应用，如环境消毒剂。
