Sublancin protects against methicillin-resistant Staphylococcus aureus infection by the combined modulation of innate immune response and microbiota.

Methicillin-resistant Staphylococcus aureus (MRSA) is a major pathogen responsible for community and hospital bacterial infections. In the present study, the protective role of sublancin, an antimicrobial peptides, was explored in MRSA infection model. We report that sublancin directly induce macrophage migration through the chemotactic receptors. We further show that sublancin exhibits protection in a mouse MRSA infection model. This protection involved an immunomodulatory activity, but was blocked by depletion of monocyte/macrophages or neutrophils. Sublancin selectively up-regulates the levels of chemokines (C-X-C motif chemokine ligand 1, CXCL1 and monocyte chemoattractant protein-1, MCP-1) while reducing the production of pro-inflammatory cytokine (tumor necrosis factor-α, TNF-α). Meanwhile, sublancin regulated the microbiota composition disrupted by MRSA injection, increasing the abundance of Lactobacillus and decreasing that of Staphylococcus and Pseudomonas. Also, sublancin restored to normal levels of metabolic functional pathways, especially amino acid biosynthesis (e.g., branched amino acid, histidine and tryptophan), disrupted after injection, and this restoration was significantly correlated with neutrophils. These results demonstrates that sublancin stimulates the innate response and modulates the microbiota community to protect against MRSA infection.