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(A...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.展开更多
基金financial support from the NSFC-BRICS(No.81861148020,H.Xie)the Fundamental Research Funds for the Central Universities(H.Xie)+1 种基金the Research Program of State Key Laboratory of Bioreactor Engineering(H.Xie)DST-BRICS multilateral cooperation project(DST/IMRCD/BRICS/PilotCall2/MBLI/2018(G))。
文摘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.
