Quaternary ammonium modified carbon quantum dots as an antimicrobial agent against gram-positive bacteria for the treatment of MRSA-infected pneumonia in mice
Quaternary ammonium modified carbon quantum dots as an antimicrobial agent against gram-positive bacteria for the treatment of MRSA-infected pneumonia in mice
复制标题
季铵修饰碳量子点作为革兰氏阳性菌抗菌剂治疗小鼠 MRSA 感染肺炎
DOI：
10.1016/j.carbon.2020.03.009
复制
发表时间：
2020
期刊：
影响因子：
10.9
通讯作者：
Xinhua Lin
中科院分区：
文献类型：
--
作者：
Chengfei Zhao;Lina Wu;Xuewen Wang;Shaohuang Weng;Zhipeng Ruan;Qicai Liu;Liqing Lin;Xinhua Lin
本文以2，3-环氧丙基三甲基氯化铵和二甲基二烯丙基氯化铵为原料，采用简单的绿色“一锅法”合成了季铵型碳量子点（QCQD）。QCQD对金黄色葡萄球菌、耐甲氧西林金黄色葡萄球菌（MRSA）、表皮葡萄球菌、单核细胞增生李斯特菌和粪肠球菌等革兰氏阳性菌均有较好的抗菌活性。QCQD治疗小鼠MRSA感染性肺炎，可促进小鼠肺部炎症消退。体内和体外毒性试验也证实了QCQD具有可接受的生物相容性。毫无疑问，所有的实验结果证实，QCQD是一个很有前途的治疗革兰氏阳性菌感染的抗菌药物。基于串联质量标签的定量蛋白质组学分析证实了QCQD的抗菌机制，QCQD可能主要作用于核糖体，上调RNA降解相关蛋白，从而干扰细菌细胞内蛋白质的翻译、翻译后修饰和蛋白质周转。蛋白质组学的应用将抗菌机制的研究从单一靶点扩展到蛋白质网络，实现了对QCQD作用细菌的多靶点研究和分析，为研发针对耐药菌的高效杀菌武器提供了新的思路和策略。
In this work, quaternary ammonium carbon quantum dots (QCQD) was successfully synthesized with 2,3-epoxypropyltrimethylammonium chloride and diallyldimethylammonium chloride by a simple green “one-pot” method. QCQD was demonstrated to have satisfactory antibacterial activity against gram-positive bacteria, includingStaphylococcus aureus, methicillin-resistantStaphylococcus aureus(MRSA),Staphylococcusepidermidis,Listera monocytogenesandEnterococcusfaecalis. QCQD was used to treat MRSA-infected pneumonia in mice, and could promote the regression of pulmonary inflammation in lung of mice. In vivo and in vitro toxicity tests also confirmed that QCQD had acceptable biocompatibility. There is no doubt that all the experimental results confirmed that QCQD is a promising antimicrobial agent for treating infections of gram-positive bacteria. The antibacterial mechanism of QCQD was analyzed and confirmed by the quantitative proteomics based tandem mass tags, revealing that QCQD might interfere with the protein translation, posttranslational modification and protein turnover in bacterial cells by mainly acting on ribosomes and upregulating RNA degradation related proteins. The application of proteomics extended the research on antibacterial mechanism from single target to protein network and realized the research and analysis on multiple targets of bacteria treated by QCQD, providing a new idea and strategy for the development of efficient bactericidal weapon against drug-resistant bacteria.