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

Jinze He1, Hong Li2, Yujuan Xu3

  • 1Sericultural and Agri-Food Research Institute, Guangdong Academy of Agricultural Sciences, Key Laboratory of Functional Foods, Ministry of Agriculture and Rural Affairs, Guangdong Key Laboratory of Agricultural Product Processing, Guangzhou, 510610, China; College of Food Science and Technology, Yunnan Agricultural University, Kunming, 650201, Yunnan, China.

Journal of Dairy Science
|February 1, 2025
PubMed

Insights

A novel milk peptide, GMp7, effectively combats Staphylococcus aureus by disrupting bacterial cell membranes and interfering with essential proteins. This peptide shows promise for enhancing food safety and extending the shelf life of dairy products.

Area of Science:

  • Microbiology
  • Biochemistry
  • Food Science

Background:

  • Antimicrobial peptides (AMPs) are crucial for innate immunity and represent a promising alternative to conventional antibiotics.
  • Staphylococcus aureus is a significant pathogen in food products, necessitating effective control strategies.
  • Identifying novel AMPs with potent antibacterial activity against S. aureus is of high importance for food safety.

Purpose of the Study:

  • To identify and characterize a novel milk-derived antimicrobial peptide, GMp7.
  • To elucidate the multi-target antibacterial mechanism of GMp7 against Staphylococcus aureus.
  • To evaluate the efficacy of GMp7 in inhibiting S. aureus growth in pasteurized milk.

Main Methods:

  • Fourier-transform infrared spectroscopy, flow cytometry, and scanning electron microscopy were used to analyze GMp7's effects on bacterial cells.
  • Label-free proteomics analysis identified protein targets and quantified proteome changes induced by GMp7.
  • Molecular docking was employed to predict binding affinities of GMp7 to key S. aureus proteins.

Main Results:

  • GMp7 possesses a secondary structure (17.45% α-helix, 20.10% β-corner, 37.13% β-fold) conducive to membrane disruption.
  • Proteomic analysis revealed GMp7 downregulates 99 proteins and upregulates 26, indicating a multi-target mechanism.
  • GMp7 binds strongly to essential S. aureus proteins asd and pcrA, with binding energies of -8.477 and -8.407 kcal/mol, respectively.
  • GMp7 interferes with peptidoglycan biosynthesis, ABC transport, 2-component systems, DNA replication, and mismatch repair.
  • GMp7 significantly inhibited S. aureus growth in pasteurized milk.

Conclusions:

  • GMp7 exhibits a potent, multi-target antibacterial mechanism against Staphylococcus aureus.
  • The peptide's ability to disrupt bacterial membranes and inhibit essential cellular processes contributes to its efficacy.
  • GMp7 demonstrates significant potential for application in the dairy industry to improve food safety and extend product shelf life.