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

• Published in: Applied microbiology and biotechnology Vol. 107; no. 21; pp. 6621 - 6640
• Main Authors: Wu, Peifen, Yang, Jie, Chen, Chi, Li, Ruili, Chen, Shunxian, Weng, Yanlin, Lin, Yayi, Chen, Zhiying, Yu, Fengfan, Lü, Xucong, Ni, Li, Han, Jinzhi
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.11.2023; Springer Nature B.V
• Subjects: Amino acids; Angiogenesis; Antimicrobial activity; Antimicrobial agents; Antimicrobial resistance; Applied Microbial and Cell Physiology; Bacteria; Biocompatibility; Biofilms; Biomedical and Life Sciences; Biotechnology; Cations; Deoxyribonucleic acid; DNA; Drug development; Drug resistance; Endotoxins; Health risks; Heterozygosity; Inflammation; Life Sciences; Methicillin; Microbial Genetics and Genomics; Microbiology; Multidrug resistance; Pathogens; Peptides; Skin; Staphylococcus aureus; Staphylococcus infections; Toxicity; Wound healing; Abhisin-like peptides; Antimicrobial activity; Arginine-rich peptides; MRSA infections; Murine wound model
• ISSN: 0175-7598; 1432-0614
• DOI: 10.1007/s00253-023-12748-1

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. Graphical Abstract