Rational design of Abhisin-like peptides enables generation of potent antimicrobial activity against pathogens.

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.

• Authors: Peifen Wu, Jie Yang, Chi Chen, Ruili Li, Shunxian Chen, Yanlin Weng, Yayi Lin, Zhiying Chen, Fengfan Yu, Xucong Lü, Li Ni, Jinzhi Han
• Journal: Applied microbiology and biotechnology (Appl Microbiol Biotechnol) Vol. 107 Issue 21 Pg. 6621-6640 (Nov 2023) ISSN: 1432-0614 [Electronic] Germany
• PMID: 37672069 (Publication Type: Journal Article)
• Copyright: © 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.