RW-BP100-4D, a Promising Antimicrobial Candidate With Broad-Spectrum Bactericidal Activity

With the rapid emergence and dissemination of antimicrobial resistance (AMR) genes in bacteria from animal, animal-derived food and human clinic, it is of great significance to develop new approaches to combat the multidrug-resistant bacteria. This study presented a short linear antimicrobial peptide RW-BP100-4D, which was derived from RW-BP100 (RRLFRRILRWL-NH2) by transforming the N-terminal 4th amino acid from L- to D-enantiomer. This modification remarkably reduced the peptide cytotoxicity to mammalian cells, as indicated by hemolytic and cytotoxicity assays. Meanwhile, the antimicrobial activity of RW-BP100-4D was improved against a more variety of Gram-positive and Gram-negative bacteria (sensitive and resistant) as well as fungi. Also, RW-BP100-4D showed strong in vitro anti-biofilm activity in a concentration-dependent manner, including inhibition of the biofilm-formation and dispersion of the mature biofilms of Staphylococcus aureus. RW-BP100-4D could be efficiently uptaken by bovine mammary epithelial cells (MAC-T) cells to eliminate the intracellular S. aureus ATCC29213 and Salmonella enterica ATCC13076. Moreover, RW-BP100-4D was highly effective in food disinfection of multiple bacterial contamination (including S. aureus, Listeria monocytogenesis, Escherichia coli O157: H7, Campylobacter jejuni, S. enterica, and Shewanella putrefaction, 3.61 +/- 0.063 log reduction) on chicken meat, and could kill 99.99% of the methicillin-resistant Staphylococcus aureus (MRSA) strain in the mouse skin infection model. In summary, RW-BP100-4D is a promising antimicrobial candidate for application on food disinfection and local infection treatment. However, the protease-sensitivity of RW-BP100-4D and toxic effect at higher doses reduced the therapeutic effect of the candidate peptide in vivo and should be improved in the future studies.

Automated summary

A new short linear antimicrobial peptide, RW-BP100-4D, was developed, showing improved antimicrobial activity against a variety of bacteria and fungi. It demonstrated potential applications in food disinfection and local infection treatment. However, further improvement is needed to reduce protease sensitivity and toxic effects at higher doses.