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

作　　者：Weipan Xu Zheng Ma Geetika Dhanda Jayanta Haldar Hexin Xie 

机构地区：[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

出　　处：《Chinese Chemical Letters》2023年第5期241-245,共5页中国化学快报（英文版）

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))。

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.

关 键 词：Antibiotic resistance Β-LACTAMASE Antimicrobial peptide CYTOTOXICITY 

分 类 号：R965[医药卫生—药理学]