AUTHOR=Tong Xingqi , Li Jun , Wei Ruicheng , Gong Lan , Ji Xing , He Tao , Wang Ran 

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

JOURNAL=Frontiers in Microbiology

VOLUME=12

YEAR=2022

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2021.815980

DOI=10.3389/fmicb.2021.815980

ISSN=1664-302X

ABSTRACT=<p>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 <sc>L</sc>- to <sc>D</sc>-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 <italic>in vitro</italic> anti-biofilm activity in a concentration-dependent manner, including inhibition of the biofilm-formation and dispersion of the mature biofilms of <italic>Staphylococcus aureus</italic>. RW-BP100-4D could be efficiently uptaken by bovine mammary epithelial cells (MAC-T) cells to eliminate the intracellular <italic>S. aureus</italic> ATCC29213 and <italic>Salmonella enterica</italic> ATCC13076. Moreover, RW-BP100-4D was highly effective in food disinfection of multiple bacterial contamination (including <italic>S. aureus</italic>, <italic>Listeria monocytogenesis</italic>, <italic>Escherichia coli</italic> O157: H7, <italic>Campylobacter jejuni</italic>, <italic>S. enterica</italic>, and <italic>Shewanella putrefaction</italic>, 3.61 ± 0.063 log reduction) on chicken meat, and could kill 99.99% of the methicillin-resistant <italic>Staphylococcus aureus</italic> (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 <italic>in vivo</italic> and should be improved in the future studies.</p>