艰难梭菌光动力抗菌化学疗法（PACT）的研发
Development of Photodynamic Antimicrobial Chemotherapy (PACT) for Clostridium difficile.
作者信息
De Sordi Luisa, Butt M Adil, Pye Hayley, Kohoutova Darina, Mosse Charles A, Yahioglu Gokhan, Stamati Ioanna, Deonarain Mahendra, Battah Sinan, Ready Derren, Allan Elaine, Mullany Peter, Lovat Laurence B
机构信息
Microbial Diseases, UCL Eastman Dental Institute, London, United Kingdom; Research Department of Tissue & Energy, UCL, London, United Kingdom.
Research Department of Tissue & Energy, UCL, London, United Kingdom; Division of Gastrointestinal Services, University College Hospital, London, United Kingdom.
出版信息
PLoS One. 2015 Aug 27;10(8):e0135039. doi: 10.1371/journal.pone.0135039. eCollection 2015.
BACKGROUND
Clostridium difficile is the leading cause of antibiotic-associated diarrhoea and pseudo membranous colitis in the developed world. The aim of this study was to explore whether Photodynamic Antimicrobial Chemotherapy (PACT) could be used as a novel approach to treating C. difficile infections.
METHODS
PACT utilises the ability of light-activated photosensitisers (PS) to produce reactive oxygen species (ROS) such as free radical species and singlet oxygen, which are lethal to cells. We screened thirteen PS against C. difficile planktonic cells, biofilm and germinating spores in vitro, and cytotoxicity of effective compounds was tested on the colorectal adenocarcinoma cell-line HT-29.
RESULTS
Three PS were able to kill 99.9% of bacteria in both aerobic and anaerobic conditions, both in the planktonic state and in a biofilm, after exposure to red laser light (0.2 J/cm2) without harming model colon cells. The applicability of PACT to eradicate C. difficile germinative spores indirectly was also shown, by first inducing germination with the bile salt taurocholate, followed by PACT.
CONCLUSION
This innovative and simple approach offers the prospect of a new antimicrobial therapy using light to treat C. difficile infection of the colon.
背景
艰难梭菌是发达国家抗生素相关性腹泻和伪膜性结肠炎的主要病因。本研究的目的是探讨光动力抗菌化疗（PACT）是否可作为治疗艰难梭菌感染的一种新方法。
方法
PACT利用光激活的光敏剂（PS）产生诸如自由基和单线态氧等活性氧（ROS）的能力，这些物质对细胞具有致死性。我们在体外筛选了13种PS对艰难梭菌浮游细胞、生物膜和萌发孢子的作用，并在结肠腺癌细胞系HT - 29上测试了有效化合物的细胞毒性。
结果
三种PS在暴露于红色激光（0.2 J/cm²）后，在有氧和无氧条件下，无论是浮游状态还是生物膜状态，都能杀死99.9%的细菌，且不损害模型结肠细胞。通过先用牛磺胆酸盐诱导萌发，然后进行PACT，还显示了PACT间接根除艰难梭菌萌发孢子的适用性。
结论
这种创新且简单的方法为利用光治疗结肠艰难梭菌感染的新型抗菌疗法提供了前景。
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