Milk-derived antimicrobial peptide GMp7: Disrupting protein networks for multi-target antibacterial inhibition and enhanced dairy preservation

ABSTRACT: Our goal was to identify and characterize a novel milk-derived antimicrobial peptide, GMp7, and reveal its antibacterial mechanism against Staphylococcus aureus. Therefore, this study revealed the multi-target antibacterial mechanism of GMp7 on S. aureus DC.RB-015 by Fourier-transform infr...

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Main Authors: Jinze He, Hong Li, Yujuan Xu, Yufang Li, Tingting Yang, Xiaoyan Yu, Xue Yang, Aixiang Huang, Yuanshan Yu, Yanan Shi
Format: Article
Language:English
Published: Elsevier 2025-04-01
Series:Journal of Dairy Science
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Online Access:http://www.sciencedirect.com/science/article/pii/S0022030225000633
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Summary:ABSTRACT: Our goal was to identify and characterize a novel milk-derived antimicrobial peptide, GMp7, and reveal its antibacterial mechanism against Staphylococcus aureus. Therefore, this study revealed the multi-target antibacterial mechanism of GMp7 on S. aureus DC.RB-015 by Fourier-transform infrared spectroscopy, flow cytometry, scanning electron microscopy, and label-free proteomics analysis. The results showed that GMp7 has a secondary structure consisting of 17.45% α-helix, 20.10% β-corner, and 37.13% β-fold, which is conducive to membrane disruption and bacterial cell death. Treatment with GMp7 induced a significant change in the proteome, resulting in the downregulation of 99 proteins and the upregulation of 26 proteins, indicating a multi-target effect on bacterial physiology. Notably, GMp7 forms stable bonds with the critical proteins asd and pcrA within the S. aureus protein network, which includes a larger network of 17 proteins essential for bacterial viability. The binding energies for GMp7 with asd and pcrA were determined to be −8.477 and −8.407 kcal/mol, respectively. GMp7 exerts its bacteriostatic effects through multiple pathways, including interference with peptidoglycan biosynthesis, ATP-binding cassette transport, the 2-component system, DNA replication, and mismatch repair. The efficacy of the peptide against S. aureus in pasteurized milk suggests its potential use in the dairy industry to improve product shelf life and safety. In addition, GMp7 significantly inhibited the growth of S. aureus in milk. These findings have practical significance for the use of antimicrobial peptides to control bacterial contamination in food and improve food safety.
ISSN:0022-0302