Selective lethal photosensitization of methicillin-resistant Staphylococcus aureus using an IgG-tin(IV) chlorin e6 conjugate
Selective lethal photosensitization of methicillin-resistant Staphylococcus aureus using an IgG-tin(IV) chlorin e6 conjugate
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DOI：
10.1093/jac/dkf209
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发表时间：
2002-12-01
影响因子：
5.2
通讯作者：
Wilson, M
中科院分区：
文献类型：
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作者：
Embleton, ML;Nair, SP;Wilson, M
目标.耐甲氧西林金黄色葡萄球菌（MRSA）对常规抗菌药物的耐药性不断增加，需要开发替代方法来预防和治疗感染。一种这样的方法是光动力疗法，其中靶细胞用光激活药物（光敏剂）处理。本研究旨在确定MRSA表达IgG结合蛋白（蛋白A）的能力是否可以利用，以使生物体与光敏剂[锡（IV）二氢卟酚e6; SnCe 6]连接到IgG的选择性致死光敏化。在IgG-SnCe 6偶联物存在下，将各种MRSA菌株暴露于氦/氖激光器的光下，并通过活菌计数对存活菌进行计数。对照品由在存在或不存在结合物的情况下辐照的混悬液和在存在结合物的情况下避光保存的混悬液组成。还使用未缀合的光敏剂进行类似的实验。使用由EMRSA-16和血链球菌组成的悬浮液重复实验。IgG-SnCe 6和SnCe 6对EMRSA-16的杀伤作用具有光剂量依赖性和光敏剂依赖性。使用相同的光能剂量和光敏剂浓度，IgG-SnCe 6比未缀合的SnCe 6实现更大的杀伤。此外，IgG-SnCe 6缀合物，而不是SnCe 6，能够在也含有S的悬浮液中选择性地杀死EMRSA-16。而后者的活菌计数没有任何减少。这些结果表明，可以使用IgG-锡（IV）二氢卟酚e6缀合物实现MRSA的选择性致死光敏化。杀灭的有效性部分取决于所用的特定MRSA菌株，临床上重要的EMRSA-16菌株是最敏感的。
Objectives. The growing resistance of methicillin-resistant Staphylococcus aureus (MRSA) to conventional antimicrobial agents necessitates the development of alternative approaches to preventing and treating infections. One such approach is photodynamic therapy, whereby target cells are treated with light-activated drugs (photosensitizers). This investigation aimed to determine whether the ability of MRSA to express the IgG-binding protein, protein A, could be exploited to enable selective lethal photosensitization of the organism with a photosensitizer [tin (IV) chlorin e6; SnCe6] linked to IgG.Methods. Various strains of MRSA were exposed to light from a helium/neon laser in the presence of an IgG-SnCe6 conjugate and the survivors enumerated by viable counting. Controls consisted of suspensions irradiated in the presence or absence of the conjugate and suspensions kept in the dark in the presence of the conjugate. Similar experiments were also carried out using the unconjugated photosensitizer. The experiments were repeated using a suspension consisting of both EMRSA-16 and Streptococcus sanguis.Results. EMRSA-16 was killed by IgG-SnCe6 and SnCe6 in a light-dose- and photosensitizer-dependent manner. Greater kills were achieved with the IgG-SnCe6 than with the unconjugated SnCe6 using the same light energy dose and photosensitizer concentration. Furthermore, the IgG-SnCe6 conjugate, but not SnCe6, was able to kill EMRSA-16 selectively in a suspension that also contained S. sanguis without any reduction in the viable count of the latter.Conclusion. These results demonstrate that selective lethal photosensitization of MRSA can be achieved using an IgG-tin (IV) chlorin e6 conjugate. The effectiveness of killing was dependent, in part, on the particular MRSA strain used, with the clinically important EMRSA-16 strain being the most susceptible.