Design of a Novel Lysine Isopeptide 1018KI11 with Potent Antimicrobial Activity as a Safe and Stable Food Preservative Candidate

Abstract

Antimicrobial peptides are potent food additive candidates, but most of them are sensitive to proteases, which limits their application. Therefore, we substituted arginine for lysine and introduced a lysine isopeptide bond to peptide IDR-1018 in order to improve its enzymatic stability. Subsequently, the protease stability and antimicrobial/antibiofilm activity of the novel peptides (1018K2−1018KI11) were investigated. The data revealed that the antienzymatic potential of 1018KI11 to bromelain and papain increased by 2−8 folds and 16 folds, respectively. The minimum inhibitory concentration (MIC) of 1018KI11 against methicillinresistant Staphylococcus aureus (MRSA) ATCC43300 and Escherichia coli (E. coli) ATCC25922 was reduced 2-fold compared to 1018K11. Mechanism exploration suggested that 1018KI11 was more effective than 1018K11 in disrupting the cell barrier and damaging genomic DNA. Additionally, 1018KI11 at certain concentration conditions (2−64 μg/mL) reduced biofilm development of MRSA ATCC43300 by 4.9−85.9%. These data indicated that novel peptide 1018KI11 is a potential food preservative candidate.