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bioRxiv · 10.1101/299305

Enhancement of Macrophage Function by the Antimicrobial Peptide Sublancin Protects Mice from Methicillin-Resistant Staphylococcus aureus

Wang, S.·Ye, Q.·Wang, K.·Zeng, X.·Huang, S.·Yu, H.·Ge, Q.·Qi, D.·Qiao, S.
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Abstract

Methicillin-resistant Staphylococcus aureus (MRSA) is the major pathogen responsible for community and hospital bacterial infections. Sublancin, a glocosylated antimicrobial peptide isolated from Bacillus subtilis 168, possesses anti-bacterial infective effects. In this study, we investigated the role and anti-infection mechanism of sublancin in a mouse model of MRSA-induced sublethal infection. Sublancin could modulate innate immunity by inducing the production of IL-1{beta}, IL-6, TNF- and nitric oxide, enhancing phagocytosis and MRSA-killing activity in both RAW264.7 cells and peritoneal macrophages. The enhanced macrophage function by the peptide in vitro correlated with stronger protective activity in vivo in the MRSA-invasive sublethal infection model. Macrophages activation by sublancin was found to be mediated through the TLR4 and the NF-{kappa}B and MAPK signaling pathways. Moreover, oral administration of sublancin increased the frequencies of CD4+ and CD8+ T cells in mesenteric lymph nodes. The protective activity of sublancin was associated with in vivo augmenting phagocytotic activity of peritoneal macrophages and partly improving T cell-mediated immunity. Macrophages thus represent a potentially pivotal and novel target for future development of innate defense regulator therapeutics againt S. aureus infection.

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Wang, S., Ye, Q., Wang, K., Zeng, X., Huang, S., Yu, H., Ge, Q., Qi, D., Qiao, S.. 2018-04-11. Enhancement of Macrophage Function by the Antimicrobial Peptide Sublancin Protects Mice from Methicillin-Resistant Staphylococcus aureus. https://doi.org/10.1101/299305

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