Bibliographic Details
| Title: |
Discovery, development and optimisation of a novel frog antimicrobial peptide with combined mode of action against drug-resistant bacteria |
| Authors: |
Jingkai Wang, Jibo Hu, Wenyuan Pu, Xiaoling Chen, Chengbang Ma, Yangyang Jiang, Tao Wang, Tianbao Chen, Chris Shaw, Mei Zhou, Lei Wang |
| Source: |
Computational and Structural Biotechnology Journal, Vol 23, Iss , Pp 3391-3406 (2024) |
| Publisher Information: |
Elsevier, 2024. |
| Publication Year: |
2024 |
| Collection: |
LCC:Biotechnology |
| Subject Terms: |
Antimicrobial peptide, Brevinin-1, Drug-resistant, LPS binding, DNA binding, Biotechnology, TP248.13-248.65 |
| More Details: |
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, Rana pipiens. 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-Ala16-[Lys4]brevinin-1pl exhibited great enhanced therapeutic efficacy in both in vitro and in vivo tests, particularly against some antibiotics-resistant Escherichia coli strains. Mechanistic studies suggest that des-Ala16-[Lys4]brevinin-1pl may exert bactericidal effects through multiple mechanisms, including membrane disruption and DNA binding. Consequently, des-Ala16-[Lys4]brevinin-1pl holds promise as a candidate for the treatment of drug-resistant Escherichia coli infections. |
| Document Type: |
article |
| File Description: |
electronic resource |
| Language: |
English |
| ISSN: |
2001-0370 |
| Relation: |
http://www.sciencedirect.com/science/article/pii/S2001037024002952; https://doaj.org/toc/2001-0370 |
| DOI: |
10.1016/j.csbj.2024.09.006 |
| Access URL: |
https://doaj.org/article/83146f4b528c4da89ecf79dd836a0700 |
| Accession Number: |
edsdoj.83146f4b528c4da89ecf79dd836a0700 |
| Database: |
Directory of Open Access Journals |
