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蓝光可清除感染小鼠皮肤擦伤处的社区获得性耐甲氧西林金黄色葡萄球菌。

Blue light eliminates community-acquired methicillin-resistant Staphylococcus aureus in infected mouse skin abrasions.

作者信息

Dai Tianhong, Gupta Asheesh, Huang Ying-Ying, Sherwood Margaret E, Murray Clinton K, Vrahas Mark S, Kielian Tammy, Hamblin Michael R

机构信息

1 Wellman Center for Photomedicine, Massachusetts General Hospital , Boston, Massachusetts.

出版信息

Photomed Laser Surg. 2013 Nov;31(11):531-8. doi: 10.1089/pho.2012.3365. Epub 2013 Feb 13.

Abstract

BACKGROUND AND OBJECTIVE

Bacterial skin and soft tissue infections (SSTI) affect millions of individuals annually in the United States. Treatment of SSTI has been significantly complicated by the increasing emergence of community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) strains. The objective of this study was to demonstrate the efficacy of blue light (415 ± 10 nm) therapy for eliminating CA-MRSA infections in skin abrasions of mice.

METHODS

The susceptibilities of a CA-MRSA strain (USA300LAC) and human keratinocytes (HaCaT) to blue light inactivation were compared by in vitro culture studies. A mouse model of skin abrasion infection was developed using bioluminescent USA300LAC::lux. Blue light was delivered to the infected mouse skin abrasions at 30 min (acute) and 24 h (established) after the bacterial inoculation. Bioluminescence imaging was used to monitor in real time the extent of infection in mice.

RESULTS

USA300LAC was much more susceptible to blue light inactivation than HaCaT cells (p=0.038). Approximately 4.75-log10 bacterial inactivation was achieved after 170 J/cm(2) blue light had been delivered, but only 0.29 log10 loss of viability in HaCaT cells was observed. Transmission electron microscopy imaging of USA300LAC cells exposed to blue light exhibited disruption of the cytoplasmic content, disruption of cell walls, and cell debris. In vivo studies showed that blue light rapidly reduced the bacterial burden in both acute and established CA-MRSA infections. More than 2-log10 reduction of bacterial luminescence in the mouse skin abrasions was achieved when 41.4 (day 0) and 108 J/cm(2) (day 1) blue light had been delivered. Bacterial regrowth was observed in the mouse wounds at 24 h after the blue light therapy.

CONCLUSIONS

There exists a therapeutic window of blue light for bacterial infections where bacteria are selectively inactivated by blue light while host tissue cells are preserved. Blue light therapy has the potential to rapidly reduce the bacterial load in SSTI.

摘要

背景与目的

在美国,细菌性皮肤及软组织感染(SSTI)每年影响数百万个体。社区获得性耐甲氧西林金黄色葡萄球菌(CA-MRSA)菌株的不断出现使SSTI的治疗变得极为复杂。本研究的目的是证明蓝光(415±10纳米)疗法在消除小鼠皮肤擦伤中CA-MRSA感染方面的疗效。

方法

通过体外培养研究比较一株CA-MRSA菌株(USA300LAC)和人角质形成细胞(HaCaT)对蓝光灭活的敏感性。使用生物发光的USA300LAC::lux建立皮肤擦伤感染小鼠模型。在细菌接种后30分钟(急性期)和24小时(已形成期)将蓝光照射到感染的小鼠皮肤擦伤处。利用生物发光成像实时监测小鼠感染程度。

结果

USA300LAC比HaCaT细胞对蓝光灭活更敏感(p=0.038)。在给予170 J/cm²蓝光后实现了约4.75个对数10的细菌灭活,但在HaCaT细胞中仅观察到0.29个对数10的活力丧失。暴露于蓝光的USA300LAC细胞的透射电子显微镜成像显示细胞质内容物破坏、细胞壁破坏和细胞碎片。体内研究表明,蓝光能迅速降低急性期和已形成期CA-MRSA感染中的细菌负荷。当给予41.4(第0天)和108 J/cm²(第1天)蓝光时,小鼠皮肤擦伤处的细菌发光减少超过2个对数10。蓝光治疗后24小时在小鼠伤口中观察到细菌再生长。

结论

对于细菌感染存在蓝光治疗窗口,在此窗口内细菌被蓝光选择性灭活而宿主组织细胞得以保留。蓝光疗法有迅速降低SSTI中细菌载量的潜力。

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