文献类型：期刊文献

中文题名：Selective inhibition of resistant bacterial pathogens using a β-lactamase-activatable antimicrobial peptide with significantly reduced cytotoxicity

作者：Weipan Xu[1];Zheng Ma[1];Geetika Dhanda[2];Jayanta Haldar[2,3];Hexin Xie[1]

机构：[1]State Key Laboratory of Bioreactor Engineering,Shanghai Key Laboratory of New Drug Design,Frontiers Science Center for Materiobiology and Dynamic Chemistry,Shanghai Frontier Science Research Base of Optogenetic Techniques for Cell Metabolism,School of Pharmacy,East China University of Science and Technology,Shanghai 200237,China;[2]Antimicrobial Research Laboratory,New Chemistry Unit,Jawaharlal Nehru Centre for Advanced Scientific Research(JNCASR),Jakkur,Bengaluru 560064,India;[3]School of Advanced Materials,Jawaharlal Nehru Centre for Advanced Scientific Research(JNCASR),Jakkur,Bengaluru 560064,India

年份：2023

卷号：34

期号：5

起止页码：241

中文期刊名：Chinese Chemical Letters

外文期刊名：中国化学快报（英文版）

收录：CSTPCD;;Scopus;CSCD:【CSCD2023_2024】；PubMed;

基金：financial support from the NSFC-BRICS(No.81861148020,H.Xie);the Fundamental Research Funds for the Central Universities(H.Xie);the Research Program of State Key Laboratory of Bioreactor Engineering(H.Xie);DST-BRICS multilateral cooperation project(DST/IMRCD/BRICS/PilotCall2/MBLI/2018(G))。

语种：英文

中文关键词：Antibiotic resistance;β-Lactamase;Antimicrobial peptide;Cytotoxicity

摘要：The expression ofβ-lactamase,particularly metallo-β-lactamase(MBL)in bacteria has caused significant resistance to clinically importantβ-lactam antibiotics,including life-saving carbapenems.Antimicrobial peptides(AMPs)have emerged as promising therapeutic agents to combat antibiotic resistance.However,the cytotoxic AMPs has been one of the major concerns for their applications in clinical practice.Herein,we report a novel cephalosporin-caged AMP,which shows significantly reduced cytotoxicity,hemolytic activity,and antibacterial activity but turns highly active against bacteria upon specific hydrolysis by the antimicrobial resistance-causativeβ-lactamase.Further investigations demonstrate thisβ-lactamaseactivatable AMP selectively inactivates resistant bacterial pathogens over susceptible bacteria.This strategy should be applicable to other AMPs as a potential solution for the treatment of infectious diseases caused byβ-lactamase-expressing pathogenic bacteria.