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使用吩噻嗪染料对鲍曼不动杆菌进行光动力灭活:体外和体内研究

Photodynamic inactivation of Acinetobacter baumannii using phenothiazinium dyes: in vitro and in vivo studies.

作者信息

Ragàs Xavier, Dai Tianhong, Tegos George P, Agut Montserrat, Nonell Santi, Hamblin Michael R

机构信息

Institut Químic de Sarrià, Universitat Ramon Llull, Barcelona, Spain.

出版信息

Lasers Surg Med. 2010 Jul;42(5):384-90. doi: 10.1002/lsm.20922.

DOI:10.1002/lsm.20922
PMID:20583252
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2935797/
Abstract

BACKGROUND AND OBJECTIVE

Phenothiazinium dyes have been reported to be effective photosensitizers inactivating a wide range of microorganisms in vitro after illumination with red light. However, their application in vivo has not extensively been explored. This study evaluates the bactericidal activity of phenothiazinium dyes against multidrug-resistant Acinetobacter baumannii both in vitro and in vivo.

STUDY DESIGN/MATERIALS AND METHODS: We report the investigation of toluidine blue O, methylene blue, 1,9-dimethylmethylene blue, and new methylene blue for photodynamic inactivation of multidrug-resistant A. baumannii in vitro. The most effective dye was selected to carry out in vivo studies using third-degree mouse burns infected with a bioluminescent A. baumannii strain, upon irradiation with a 652 nm noncoherent light source. The mice were imaged daily for 2 weeks to observe differences in the bioluminescence-time curve between the photodynamic therapy (PDT)-treated mice in comparison with untreated burns.

RESULTS

All the dyes were effective in vitro against A. baumannii after 30 J/cm(2) irradiation of 635 or 652 nm red light had been delivered, with more effective killing when the dye remained in solution. New methylene blue was the most effective of the four dyes, achieving a 3.2-log reduction of the bacterial luminescence during PDT in vivo after 360 J/cm(2) and an 800 microM dye dose. Moreover, a statistically significant reduction of the area under the bioluminescence-time curve of PDT-treated mice was observed showing that the infection did not recur after PDT.

CONCLUSIONS

Phenothiazinium dyes, and especially new methylene blue, are potential photosensitizers for PDT to treat burns infected with multidrug-resistant A. baumannii in vivo.

摘要

背景与目的

据报道,吩噻嗪染料是有效的光敏剂,在红光照射后可在体外灭活多种微生物。然而,它们在体内的应用尚未得到广泛探索。本研究评估了吩噻嗪染料对多重耐药鲍曼不动杆菌的体内外杀菌活性。

研究设计/材料与方法:我们报告了对甲苯胺蓝O、亚甲蓝、1,9-二甲基亚甲蓝和新亚甲蓝用于体外多重耐药鲍曼不动杆菌光动力灭活的研究。选择最有效的染料,使用感染了生物发光鲍曼不动杆菌菌株的三度小鼠烧伤模型,在652nm非相干光源照射下进行体内研究。对小鼠进行为期2周的每日成像,以观察光动力疗法(PDT)治疗的小鼠与未治疗烧伤的小鼠之间生物发光-时间曲线的差异。

结果

在给予635或652nm红光30J/cm²照射后,所有染料在体外对鲍曼不动杆菌均有效,当染料保持在溶液中时杀菌效果更佳。新亚甲蓝是四种染料中最有效的,在360J/cm²和800μM染料剂量下,体内PDT过程中细菌发光降低了3.2个对数。此外,观察到PDT治疗小鼠的生物发光-时间曲线下面积有统计学意义的减少,表明PDT后感染未复发。

结论

吩噻嗪染料,尤其是新亚甲蓝,是用于体内治疗多重耐药鲍曼不动杆菌感染烧伤的PDT潜在光敏剂。

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本文引用的文献

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Photodynamic therapy for Acinetobacter baumannii burn infections in mice.光动力疗法治疗小鼠鲍曼不动杆菌烧伤感染
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Extensively drug-resistant Acinetobacter baumannii.广泛耐药鲍曼不动杆菌
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In vivo killing of Staphylococcus aureus using a light-activated antimicrobial agent.使用光激活抗菌剂在体内杀灭金黄色葡萄球菌。
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Antimicrobial photodynamic efficacy of side-chain functionalized benzo[a]phenothiazinium dyes.侧链功能化苯并[a]吩噻嗪鎓染料的抗菌光动力疗效
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Why are we afraid of Acinetobacter baumannii?我们为什么害怕鲍曼不动杆菌?
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Effect of Ca+ on the photobactericidal efficacy of methylene blue and toluidine blue against gram-negative bacteria and the dye affinity for lipopolysaccharides.钙离子对亚甲蓝和甲苯胺蓝针对革兰氏阴性菌的光杀菌效果及染料对脂多糖亲和力的影响。
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