1. Rational design of Abhisin-like peptides enables generation of potent antimicrobial activity against pathogens.
- Author
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Wu, Peifen, Yang, Jie, Chen, Chi, Li, Ruili, Chen, Shunxian, Weng, Yanlin, Lin, Yayi, Chen, Zhiying, Yu, Fengfan, Lü, Xucong, Ni, Li, and Han, Jinzhi
- Subjects
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ENDOTOXINS , *ANTI-infective agents , *CATHELICIDINS , *PEPTIDES , *METHICILLIN-resistant staphylococcus aureus , *PATHOGENIC bacteria , *BACTERICIDAL action - Abstract
Infections caused by pathogens can be a significant challenge in wound healing, particularly when antimicrobial resistance is a factor. This can pose a serious threat to human health and well-being. In this scenario, it is imperative to explore novel antimicrobial agents to fight against multi-drug resistant (MDR) pathogenic bacteria. This study employed rational design strategies, including truncation, amino acid replacement, and heterozygosity, to obtain seven α-helical, cationic, and engineered peptides based on the original template of Abhisin. Among the analogs of Abhisin, AB7 displayed broad-spectrum and potent antimicrobial activity, superior targeting of membranes and DNA, and the ability to disrupt biofilms and anti-endotoxins in vitro. Additionally, we evaluated the anti-infection ability of AB7 using a murine skin wound model infected with methicillin-resistant Staphylococcus aureus (MRSA) and found that AB7 displayed negligible toxicity both in vitro and in vivo. Furthermore, AB7 exhibited desirable therapeutic efficacy by reducing bacterial burden and pro-inflammatory mediators, modulating cytokines, promoting wound healing, and enhancing angiogenesis. These results highlight the potential of AB7 as a promising candidate for a new antibiotic. Key points: • A α-helical, cationic, and engineered peptide AB7 was obtained based on Abhisin. • AB7 exhibited potent antimicrobial activity and multiple bactericidal actions. • AB7 effectively treated infected skin wounds in mice. [ABSTRACT FROM AUTHOR]
- Published
- 2023
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