文献类型：期刊文献

英文题名：Selective inhibition of resistant bacterial pathogens using a ,B-lactamase-activatable antimicrobial peptide with significantly re duce d cytotoxicity

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

机构：[1]East China Univ Sci & Technol, Frontiers Sci Ctr Materiobiol & Dynam Chem, Shanghai Key Lab New Drug Design, State Key Lab Bioreactor Engn,Sch Pharm,Shanghai F, Shanghai 200237, Peoples R China;[2]Jawaharlal Nehru Ctr Adv Sci Res JNCASR, New Chem Unit, Antimicrobial Res Lab, Bengaluru 560064, India;[3]Jawaharlal Nehru Ctr Adv Sci Res JNCASR, Sch Adv Mat, Bengaluru 560064, India

年份：2023

卷号：34

期号：5

外文期刊名：CHINESE CHEMICAL LETTERS

收录：;WOS:【SCI-EXPANDED(收录号:WOS:000956479600001)】；

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

语种：英文

外文关键词：Antibiotic resistance; B -Lactamase; Antimicrobial peptide; Cytotoxicity

摘要：The expression of ,B-lactamase, particularly metallo- ,B-lactamase (MBL) in bacteria has caused significant resistance to clinically important ,B-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-causative ,B-lactamase. Further investigations demonstrate this ,B-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 by ,B-lactamase-expressing pathogenic bacteria. (c) 2023 Published by Elsevier B.V. on behalf of Chinese Chemical Society and Institute of Materia Medica, Chinese Academy of Medical Sciences.