Blue Light Eliminates Community-Acquired Methicillin-Resistant Staphylococcus aureus in Infected Mouse Skin Abrasions
Blue Light Eliminates Community-Acquired Methicillin-Resistant Staphylococcus aureus in Infected Mouse Skin Abrasions
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DOI：
10.1089/pho.2012.3365
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发表时间：
2013-11-01
影响因子：
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通讯作者：
Hamblin, Michael R.
中科院分区：
文献类型：
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作者：
Dai, Tianhong;Gupta, Asheesh;Hamblin, Michael R.
背景和目的：细菌性皮肤和软组织感染 (SSTI) 每年影响美国数百万人。由于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，SSTI 的治疗变得非常复杂。本研究的目的是证明蓝光（415 +/- 10nm）疗法对于消除小鼠皮肤擦伤中 CA-MRSA 感染的功效。方法：通过体外培养研究比较 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 USA300LAC::lux 开发了皮肤擦伤感染的小鼠模型。细菌接种后 30 分钟（急性）和 24 小时（建立）将蓝光照射到受感染的小鼠皮肤擦伤处。使用生物发光成像实时监测小鼠的感染程度。结果：USA300LAC 比 HaCaT 细胞更容易受到蓝光失活的影响 (p=0.038)。 170J/cm(2) 蓝光照射后，细菌灭活率约为 4.75-log(10)，但 HaCaT 细胞活力仅损失 0.29 log(10)。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的破坏、细胞壁的破坏和细胞碎片。体内研究表明，蓝光可迅速减少急性和已确诊的 CA-MRSA 感染中的细菌负荷。当照射 41.4（第 0 天）和 108J/cm(2)（第 1 天）蓝光时，小鼠皮肤擦伤处的细菌发光减少超过 2-log(10)。蓝光治疗24小时后，在小鼠伤口中观察到细菌再生。结论：蓝光对于细菌感染存在一个治疗窗口，其中细菌被蓝光选择性灭活，同时保留宿主组织细胞。蓝光疗法有可能快速减少 SSTI 中的细菌负荷。
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 +/- 10nm) 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 30min (acute) and 24h (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-log(10) bacterial inactivation was achieved after 170J/cm(2) blue light had been delivered, but only 0.29 log(10) 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-log(10) reduction of bacterial luminescence in the mouse skin abrasions was achieved when 41.4 (day 0) and 108J/cm(2) (day 1) blue light had been delivered. Bacterial regrowth was observed in the mouse wounds at 24h 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.