Scientists made shorter, more stable versions of the natural immune peptide LL‑37. Some of these new peptides kill a range of tough, drug‑resistant bacteria (the ESKAPE group) better than the original and cause less damage to red blood cells. One version, called 17tF‑W, cleared MRSA infections in mouse catheters and changed immune signals in the tissue.

Antimicrobial peptides are essential components of innate immune systems that protect hosts from infection. They are also useful candidates for developing a new generation of antibiotics to fight antibiotic-resistant pathogens. Human innate immune peptide LL-37 can inhibit biofilm formation, but suffers from high cost due to a long peptide length and rapid protease degradation. To improve the peptide, we previously identified the major active region and changed the peptide backbone structure. This study designed two families of new peptides by altering peptide side chains. Interestingly, these peptides displayed differential potency against various ESKAPE pathogens in vitro and substantially reduced hemolysis. Further potency test in vivo revealed that 17tF-W eliminated the burden of methicillin-resistant Staphylococcus aureus (MRSA) USA300 in both mouse-embedded catheters and their surrounding tissues. In addition, peptide treatment suppressed the level of chemokine TNFα, and boosted the levels of chemokines MCP-1, IL-17A and IL-10 in the surrounding tissues of the infected catheter embedded in mice. In conclusion, we have designed a set of new LL-37 peptides with varying antimicrobial activities, opening the door to potential topical treatment of infections involving different drug-resistant pathogens.