Cathelicidins Mitigate Staphylococcus aureus Mastitis and Reduce Bacterial Invasion in Murine Mammary Epithelium

Abstract

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