Using tea nanoclusters asβ-lactamase inhibitors to cure multidrug-resistant bacterial pneumonia:A promising therapeutic strategy by Chinese materioherbology  

作　　者：Ziao Zhou Jun Li Lei Tan Xiangmei Liu Yufeng Zheng Zhenduo Cui Changyi Li Kelvin Wai Kwok Yeung Zhaoyang Li Yanqin Liang Shengli Zhu Shuilin Wu 

机构地区：[1]Biomedical Materials Engineering Research Center,Collaborative Innovation Center for Advanced Organic Chemical Materials Co-constructed by the Province and Ministry,Hubei Key Laboratory of Polymer Materials,Ministry-of-Education Key Laboratory for the Green Preparation and Application of Functional Materials,School of Materials Science&Engineering,Hubei University,Wuhan 430062,China [2]School of Materials Science&Engineering,Peking University,Beijing 100871,China [3]School of Materials Science&Engineering,the Key Laboratory of Advanced Ceramics and Machining Technology by the Ministry of Education of China,Tianjin University,Tianjin 300072,China [4]Stomatological Hospital,Tianjin Medical University,No.12,Qixiangtai Road,Heping District,Tianjin 300070,China [5]Department of Orthopaedics&Traumatology,Li Ka Shing Faculty of Medicine,The University of Hong Kong,Pokfulam,Hong Kong 999077,China

出　　处：《Fundamental Research》2022年第3期496-504,共9页自然科学基础研究（英文版）

基　　金：This work was jointly supported by the China National Funds for Distinguished Young Scientists(Grant No.51925104);National Natural Science Foundation of China(Grants No.51871162 and 52173251);RGC/NSFC(Grant No.N_HKU725-1616);Hong Kong ITC(Grants No.ITS/287/17,GHX/002/14SZ);Health and Medical Research Fund(Grant No.03142446).

摘　　要：β-lactamase,a kind of hydrolase in multi-drug resistant pathogens,can hydrolyzeβ-lactam antibiotics and make these kinds of antibiotics invalid.Small-molecular inhibitors about the enzyme and their mechanism are widely investigated but they may result in unavoidable adverse reactions and drug-resistance.Herein,we propose a new therapeutic strategy of Chinese materioherbology,in which herbal medicine or traditional Chinese medicinal herbs can be employed as biological functional materials or refreshed/excited by means of materialogy.Nat-ural tea nanoclusters(TNCs)were extracted from tea to inhibitβ-lactamase.Different from the mechanism of small-molecular inhibitors inhibiting enzymes by binding to the corresponding active sites,the TNCs as a cap cover the protein pocket and create a spatial barrier between the active sites and antibiotics,which was named“capping-pocket”effect.TNCs were combined with amoxicillin sodium(Amo)to treat the methicillin-resistant Staphylococcus aureus(MRSA)pneumonia in mice.This combinatorial therapy remarkably outperforms antibiotic monotherapy in reducing MRSA infections and the associated inflammation in mice.The therapeutic strategy exhibited excellent biosafety,without any side effects,even in piglets.Hence,TNCs have great clinical value in potentiatingβ-lactam antibiotic activity for combatting multi-drug resistant pathogen infections and the"pocket capping"effect can guide the design of new enzyme inhibitors in near future.

关 键 词：Materioherbology Antibacterial β-Lactam antibiotic PNEUMONIA Tea nanoclusters 

分 类 号：R28[医药卫生—中药学] R563.1[医药卫生—中医学]