An engineered antimicrobial peptide Z-FV7 demonstrates bactericidal efficacy against multidrug-resistant Escherichia coli in a murine model of endometritis.

Abstract

Endometritis is a common reproductive disorder in dairy cows, with antibiotics being the primary treatment option. However, the overuse of antibiotics has contributed to the growing problem of antimicrobial resistance. Antimicrobial peptides (AMPs) have been widely studied for their ability to kill bacteria and modulate immune responses. Previous research has focused on modifying natural AMPs extracted from Zophabas atratus haemolymph; however, these peptides have displayed limited effectiveness against bacteria. To overcome this limitation, researchers engineered a modified AMP, Z-FV7, by incorporating the sequence of the human-derived AMP LL-37. The resulting peptide demonstrated a favourable safety profile, with a minimum inhibitory concentration (MIC) reduced to 32 μg/mL and improved antibacterial activity against pathogens such as Staphylococcus aureus and Pseudomonas aeruginosa. Z-FV7 was tested in a bovine uterine epithelial cell model infected with Escherichia coli and in a murine model of endometritis. The findings showed that Z-FV7 alleviated clinical symptoms, inhibited the activation of the NF-κB signalling pathway induced by drug-resistant E. coli, reduced the expression of pro-inflammatory cytokines (TNF-α, IL-1β, IL-6), and promoted the expression of tight junction proteins (Claudin-1 and ZO-1). These results indicated that Z-FV7 can help reduce uterine inflammation and provide therapeutic outcomes similar to those of antibiotics during E. coli infection. Overall, Z-FV7 holds promise as a potential alternative to antibiotics for treating endometriosis in the future.