Scientists found a new short peptide called LL-37mini that kills tough bacteria like MRSA, E. coli, and Pseudomonas without harming human cells and can break down bacterial biofilms, but it’s still in early animal testing and not yet a consumer product.

Identification of novel antibiotics is of top importance because of the threat of antibiotic-resistant pathogens. Antimicrobial screening in Mueller-Hinton broth is frequently the first step in antimicrobial discovery. Although widely utilized, this medium is not ideal as it could mask activity of candidates such as human cathelicidin LL-37 against methicillin-resistant <i>Staphylococcus aureus</i> (MRSA). This study identified a sensitive medium where LL-37 displayed excellent activity against numerous pathogens, including MRSA. Our screen of ultrashort overlapping LL-37 peptides in this medium led to the identification of KR-8, four residues shorter than KR-12. Hence, our screen condition may increase positive compound hits during antimicrobial screening. KR-8 provided an appealing template for us to design LL-37mini, which was potent against MRSA, <i>Escherichia coli</i>, and <i>Pseudomonas aeruginosa</i> but not toxic to mammalian cells. LL-37mini also inhibited bacterial attachment and biofilm formation and disrupted preformed biofilms <i>in vitro</i> and killed MRSA in murine wound biofilms <i>in vivo</i>. Consistent with membrane targeting, MRSA failed to develop resistance to LL-37mini in a multiple-passage experiment. Because LL-37mini can be made cost effectively, it can be developed into new antibiofilm and antimicrobial agents.