Citation: Weipan Xu, Zheng Ma, Geetika Dhanda, Jayanta Haldar, Hexin Xie. Selective inhibition of resistant bacterial pathogens using a β-lactamase-activatable antimicrobial peptide with significantly reduced cytotoxicity[J]. Chinese Chemical Letters, ;2023, 34(5): 107847. doi: 10.1016/j.cclet.2022.107847 shu

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

Weipan Xu ^a ,
Zheng Ma ^a ,
Geetika Dhanda ^b ,
Jayanta Haldar ^{b, c} ,
Hexin Xie ^{a, *,}

a.
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
b.
Antimicrobial Research Laboratory, New Chemistry Unit, Jawaharlal Nehru Centre for Advanced Scientific Research (JNCASR), Jakkur, Bengaluru 560064, India
c.
School of Advanced Materials, Jawaharlal Nehru Centre for Advanced Scientific Research (JNCASR), Jakkur, Bengaluru 560064, India

xiehexin@ecust.edu.cn

Received Date: 9 June 2022
Revised Date: 21 September 2022
Accepted Date: 22 September 2022
Available Online: 27 September 2022

Figures(5)

The expression of β-lactamase, particularly metallo-β-lactamase (MBL) in bacteria has caused significant resistance to clinically important β-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 β-lactamase. Further investigations demonstrate this β-lactamase-activatable 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 β-lactamase-expressing pathogenic bacteria.
- Antibiotic resistance,
- β-Lactamase,
- Antimicrobial peptide,
- Cytotoxicity
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