A novel antimicrobial peptide MP-4: Insights into its antimicrobial properties and intestinal regulation on E. coli-infected mice

The quest for novel, potent antimicrobial agents with low resistance potential poses a significant challenge for the advancement of the food and medical sectors. This study aimed to elucidate the antibacterial potency of antimicrobial peptides derived from koumiss in a murine model. Leveraging an antimicrobial peptide database, six peptides (MP-1 to MP-6) were meticulously predicted and screened for their antibacterial properties. These peptides were subsequently synthesized using chemical solid-phase methods and their antibacterial activities were rigorously validated. Remarkably, among the six peptides, MP-4 demonstrated a profound antibacterial effect against E. coli, achieving rapid bacterial eradication within 240 min. Flow cytometry analysis further corroborated its significant bactericidal activity. In vivo experiments conducted on mice infected with E. coli revealed that oral administration of MP-4 significantly ameliorated symptoms such as lethargy, anorexia, and weight loss. Additionally, it effectively reduced the colonic E. coli burden, attenuated inflammatory responses, and favorably modulated the intestinal microbiota composition. This study not only validates the robust antibacterial activity of the koumiss-derived antimicrobial peptide MP-4, but also underscores its potential therapeutic application in mitigating E. coli infections and promoting intestinal health.