A potential food biopreservative, CecXJ-37N, non-covalently intercalates into the nucleotides of bacterial genomic DNA beyond membrane attack

The antibacterial activities and mechanism of an amide-modified peptide CecXJ-37N were investigated in this study. CecXJ-37N showed small MICs (0.25-7.8 μM) against eight harmful strains common in food industry. The α-helix proportion of CecXJ-37N increased by 11-fold in prokaryotic membrane comparable environments; cytotoxicity studies demonstrated the MHC was significantly higher than that of non-amidated isoform. Moreover, CecXJ-37N possessed stronger capacities to resist trypsin and pepsin hydrolysis within two hours. Flow cytometry and scanning electron microscopy demonstrated that CecXJ-37N induced pore-formation, morphological changes, and lysed E. coli cells. Fluorescence microscopy indicated that CecXJ-37N penetrated E. coli membrane and accumulated in cytoplasm. Further ultraviolet-visible spectroscopy suggested that CecXJ-37N changed the action mode of parental peptide interacting with bacterial genome from outside binding to a tightly non-covalent intercalation into nucleotides. Overall, this study suggested that amide-modification enhanced antimicrobial activity and reduced the cytotoxicity, thus could be potential strategies for developing novel food preservatives.