In mice, the natural antimicrobial peptide LL‑37 (and its mouse version) helps fight Staph aureus infections in the breast tissue. Mice that can’t make this peptide get worse infections, while giving a synthetic version reduces bacterial entry into cells and even kills the bacteria in lab dishes. The work suggests LL‑37 could be a useful anti‑infection tool, but it’s still early‑stage and only tested in animals.

<i>Staphylococcus aureus</i>, an important cause of mastitis in mammals, is becoming increasingly problematic due to the development of resistance to conventional antibiotics. The ability of <i>S. aureus</i> to invade host cells is key to its propensity to evade immune defense and antibiotics. This study focuses on the functions of cathelicidins, small cationic peptides secreted by epithelial cells and leukocytes, in the pathogenesis of <i>S. aureus</i> mastitis in mice. We determined that endogenous murine cathelicidin (CRAMP; <i>Camp</i>) was important in controlling <i>S. aureus</i> infection, as cathelicidin knockout mice (<i>Camp^-/-</i> ) intramammarily challenged with <i>S. aureus</i> had higher bacterial burdens and more severe mastitis than did wild-type mice. The exogenous administration of both a synthetic human cathelicidin (LL-37) and a synthetic murine cathelicidin (CRAMP) (8&#x2009;&#x3bc;M) reduced the invasion of <i>S. aureus</i> into the murine mammary epithelium. Additionally, this exogenous LL-37 was internalized into cultured mammary epithelial cells and impaired <i>S. aureus</i> growth <i>in vitro</i> We conclude that cathelicidins may be potential therapeutic agents against mastitis; both endogenous and exogenous cathelicidins conferred protection against <i>S. aureus</i> infection by reducing bacterial internalization and potentially by directly killing this pathogen.