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.
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All data generated or analyzed during this study are included in this published article (and its supplementary information files).
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This study is supported by the Fujian Provincial Natural Science Foundation (No. 2020J01492).
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P W and J H conceived and designed research. J Y, C C, R L, S C, and Y W conducted experiments. Y L, Z C, and F Y analyzed data. J H and X L wrote the manuscript. W Z and N L provided the modification of this manuscript. All authors read and approved the manuscript.
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This study was approved by the Ethics Committee of the Fuzhou University. All procedures performed in studies involving animals were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. In addition, all the experiments involved in pathogenic bacteria were conducted in the Biosafety Level II Laboratory. This article does not contain any studies with humans performed by any of the authors. Informed consent was obtained from all individual participants included in the study.
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Wu, P., Yang, J., Chen, C. et al. Rational design of Abhisin-like peptides enables generation of potent antimicrobial activity against pathogens. Appl Microbiol Biotechnol 107, 6621–6640 (2023). https://doi.org/10.1007/s00253-023-12748-1
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DOI: https://doi.org/10.1007/s00253-023-12748-1