The O-acetylation on phage tail-spike protein digested penta-saccharide from Acinetobacter baumannii SK44 plays a...

Acinetobacter baumannii is a worldwide health-threaten pathogen bacteria due to antibiotic resistant and the bacterial exopolysaccharide is an attractive to develop therapeutic alternative. A. baumannii strain SK44 (Ab-SK44) is a minor antibiotic resistant clinical isolate and its exopolysaccharide (EPS) can be digested by phage tail-spike protein (TSP) into a penta-saccharide-repeat unit, which is comprised of trisaccharide {→3)Gal(β1 → 6)Glc(β1 → 3)GalNAc(α1→} as main chain with two branched GlcNAc3NAcA4OAc and GlcNAc attached to Gal. Notably, TSP digested penta-saccharide could stimulate murine macrophage Raw264.7 cells to release interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α), similar to the effect observed with Ab-SK44 EPS. Knocked-down the Toll-like receptor 4 (TLR4) on Raw264.7 diminished cytokine release, indicating that TLR4 is a critical receptor of Ab-SK44 EPS/TSP-digested penta-saccharide. O-acetyl group on TSP-digested penta-saccharide probably interacts with F126 in TLR4/Myeloid differentiation factor-2 (MD2) complex to form π-π stacking with Y131, which activate immune response. Here, we explored the mechanism of bacterial oligosaccharide-immune stimulation and shed the light on the vaccination or immune based therapy against pathogenic bacteria infection.