Antimicrobial peptide Mastoparan X has good activity against Escherichia coli in vitro and alleviates its pathogenicity in mice

Abstract Background Escherichia coli is a facultative anaerobic bacterium that normally resides in the gastrointestinal tract of humans and animals but can cause diarrhea and enteritis. MPX is an antimicrobial peptide extracted from wasp venom and has potent bactericidal effects against many bacteria. This study aimed to investigate the mechanism of MPX’s bactericidal activity against E. coli in vitro, its effect on IPEC-J2 cell apoptosis and barrier function, and its therapeutic efficacy against E. coli infection in mice. Methods The effects of MPX on E. coli were investigated in vitro, at the cellular level, and in vivo. Results The study found that the MIC of MPX against E. coli was 31.25 µg/mL, and scanning electron microscopy showed that MPX caused the bacteria to become smaller in size with leaked contents. Additionally, NPN, PI, and DiSC3(5) results showed that MPX positively correlated with the fluorescence intensity. MPX significantly inhibited E. coli biofilm formation. Furthermore, MPX effectively reduced IPEC-J2 cell apoptosis, regulated ZO-1, Occludin, and Claudin-1 expression through the Rac1 pathway, and alleviated the pathological damage in the intestine, as shown by H&E staining results. qRT-PCR results indicated that MPX increased TFF3 mRNA expression in the jejunum and colon. Conclusions This study is the first to explore the mechanism of MPX's bactericidal activity against E. coli in vitro, providing a foundation for developing new drugs to treat bacterial infections. Graphical Abstract