Cathelicidin Mitigates Staphylococcus Aureus Mouse Mastitis and Prevents Bacterial Invasion in Mammary Epithelial Cells
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2019-08-23
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Staphylococcus aureus is an important cause of mastitis, increasingly problematic due to the presence of bacterial strains resistant to conventional antibiotics. The ability of S. aureus to invade host cells is key to its ability to escape immune defense and antibiotics. This study focused on functions of cathelicidin, a small cationic peptide secreted by epithelial cells and leukocytes, in the pathogenesis of S. aureus mastitis. We determined that endogenous murine cathelicidin (CRAMP; Camp) was key in controlling S. aureus infection, as cathelicidin knockout mice (Camp-/-) inframammary challenged with S. aureus had higher bacteria burden and more severe mastitis compared to wild-type mice. Both human and murine cathelicidins, LL37 and CRAMP, respectively, reduced invasion of S. aureus in mammary epithelia. This function was independent of TLR2 and CD36 cell surface expression. LL-37 internalized into mammary epithelial cells and impaired S. aureus growth in vitro. We conclude that cathelicidins are promising anti-infectious therapeutic targets in mastitis; endogenous or exogenous cathelicidins protected against S. aureus infection by preventing internalization and potentially by directly killing this pathogen.
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Cavalcante, P. (2019). Cathelicidin Mitigates Staphylococcus Aureus Mouse Mastitis and Prevents Bacterial Invasion in Mammary Epithelial Cells (Master's thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca.