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Photo‐Disassembly of Membrane Microdomains Revives Conventional Antibiotics against MRSA
Advanced Science ( IF 14.3 ) Pub Date : 2020-01-27 , DOI: 10.1002/advs.201903117 Jie Hui 1, 2 , Pu-Ting Dong 2, 3 , Lijia Liang 1, 4 , Taraknath Mandal 3 , Junjie Li 1, 2 , Erlinda R Ulloa 5, 6 , Yuewei Zhan 7 , Sebastian Jusuf 7 , Cheng Zong 1, 2 , Mohamed N Seleem 8 , George Y Liu 5, 9 , Qiang Cui 3, 7 , Ji-Xin Cheng 1, 2, 3, 7
Advanced Science ( IF 14.3 ) Pub Date : 2020-01-27 , DOI: 10.1002/advs.201903117 Jie Hui 1, 2 , Pu-Ting Dong 2, 3 , Lijia Liang 1, 4 , Taraknath Mandal 3 , Junjie Li 1, 2 , Erlinda R Ulloa 5, 6 , Yuewei Zhan 7 , Sebastian Jusuf 7 , Cheng Zong 1, 2 , Mohamed N Seleem 8 , George Y Liu 5, 9 , Qiang Cui 3, 7 , Ji-Xin Cheng 1, 2, 3, 7
Affiliation
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Confronted with the rapid evolution and dissemination of antibiotic resistance, there is an urgent need to develop alternative treatment strategies for drug‐resistant pathogens. Here, an unconventional approach is presented to restore the susceptibility of methicillin‐resistant S. aureus (MRSA) to a broad spectrum of conventional antibiotics via photo‐disassembly of functional membrane microdomains. The photo‐disassembly of microdomains is based on effective photolysis of staphyloxanthin, the golden carotenoid pigment that gives its name. Upon pulsed laser treatment, cell membranes are found severely disorganized and malfunctioned to defense antibiotics, as unveiled by membrane permeabilization, membrane fluidification, and detachment of membrane protein, PBP2a. Consequently, the photolysis approach increases susceptibility and inhibits development of resistance to a broad spectrum of antibiotics including penicillins, quinolones, tetracyclines, aminoglycosides, lipopeptides, and oxazolidinones. The synergistic therapy, without phototoxicity to the host, is effective in combating MRSA both in vitro and in vivo in a mice skin infection model. Collectively, this endogenous chromophore‐targeted phototherapy concept paves a novel platform to revive conventional antibiotics to combat drug‐resistant S. aureus infections as well as to screen new lead compounds.
中文翻译：
膜微区的光分解使传统抗生素能够对抗 MRSA
面对抗生素耐药性的快速演变和传播，迫切需要开发针对耐药病原体的替代治疗策略。在此，提出了一种非常规方法，通过功能性膜微域的光分解来恢复耐甲氧西林金黄色葡萄球菌（MRSA）对广谱常规抗生素的敏感性。微域的光分解基于葡萄球菌黄素的有效光解，葡萄球菌黄素是一种金色的类胡萝卜素色素，因此得名。在脉冲激光治疗后，发现细胞膜严重混乱，无法防御抗生素，如膜透化、膜流化和膜蛋白 PBP2a 分离所揭示的那样。因此，光解方法增加了敏感性并抑制对广谱抗生素（包括青霉素、喹诺酮类、四环素类、氨基糖苷类、脂肽和恶唑烷酮类）产生耐药性。这种协同疗法对宿主没有光毒性，在小鼠皮肤感染模型的体外和体内都能有效对抗 MRSA。总的来说，这种内源性发色团靶向光疗概念为复兴传统抗生素以对抗耐药金黄色葡萄球菌感染以及筛选新的先导化合物奠定了一个新的平台。
更新日期：2020-01-27
中文翻译：
膜微区的光分解使传统抗生素能够对抗 MRSA
面对抗生素耐药性的快速演变和传播，迫切需要开发针对耐药病原体的替代治疗策略。在此，提出了一种非常规方法，通过功能性膜微域的光分解来恢复耐甲氧西林金黄色葡萄球菌（MRSA）对广谱常规抗生素的敏感性。微域的光分解基于葡萄球菌黄素的有效光解，葡萄球菌黄素是一种金色的类胡萝卜素色素，因此得名。在脉冲激光治疗后，发现细胞膜严重混乱，无法防御抗生素，如膜透化、膜流化和膜蛋白 PBP2a 分离所揭示的那样。因此，光解方法增加了敏感性并抑制对广谱抗生素（包括青霉素、喹诺酮类、四环素类、氨基糖苷类、脂肽和恶唑烷酮类）产生耐药性。这种协同疗法对宿主没有光毒性，在小鼠皮肤感染模型的体外和体内都能有效对抗 MRSA。总的来说，这种内源性发色团靶向光疗概念为复兴传统抗生素以对抗耐药金黄色葡萄球菌感染以及筛选新的先导化合物奠定了一个新的平台。
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