Discovery, Development and Optimisation of a Novel Frog Antimicrobial Peptide with Combined Mode of Action Against Drug-resistant Bacteria

Overview

Journal Comput Struct Biotechnol J

Specialty Biotechnology

Date 2024 Sep 30

PMID 39345903

Authors

Jingkai Wang

Jibo Hu

Wenyuan Pu

Xiaoling Chen

Chengbang Ma

Yangyang Jiang

Tao Wang

Tianbao Chen

Chris Shaw

Mei Zhou

Lei Wang

Affiliations

Soon will be listed here.

Abstract

Antimicrobial peptides (AMP) have emerged as promising candidates for addressing the clinical challenges posed by the rapid evolution of antibiotic-resistant microorganisms. Brevinins, a representative frog-derived AMP family, exhibited broad-spectrum antimicrobial activities, attacking great attentions in previous studies. However, their strong haemolytic activity and cytotoxicity, greatly limit their further development. In this work, we identified and characterised a novel brevinin-1 peptide, brevinin-1pl, from the skin secretions of the northern leopard frog, . Like many brevinins, brevinin-1pl also displayed strong haemolytic activity, resulting in a lower therapeutic index. We employed several bioinformatics tools to analyse the structure and potential membrane interactions of brevinin-1pl, leading to a series of modifications. Among these analogues, des-Ala-[Lys]brevinin-1pl exhibited great enhanced therapeutic efficacy in both and tests, particularly against some antibiotics-resistant strains. Mechanistic studies suggest that des-Ala-[Lys]brevinin-1pl may exert bactericidal effects through multiple mechanisms, including membrane disruption and DNA binding. Consequently, des-Ala-[Lys]brevinin-1pl holds promise as a candidate for the treatment of drug-resistant infections.

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