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- Lee, I-Ming, et al.
(författare)
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A hexasaccharide from capsular polysaccharide of carbapenem-resistant Klebsiella pneumoniae KN2 is a ligand of Toll-like receptor 4
- 2022
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Ingår i: Carbohydrate Polymers. - : ELSEVIER SCI LTD. - 0144-8617 .- 1879-1344. ; 278
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Tidskriftsartikel (refereegranskat)abstract
- Klebsiella pneumoniae serotype KN2 is a carbapenem-resistant strain and leads to the health care-associated in-fections, such as bloodstream infections. Its capsular polysaccharide (CPS) was isolated and cleaved by a specific enzyme from a bacteriophage into a hexasaccharide-repeating unit. With GC-MS, NMR, and Mass analyses, the structure of KN2 CPS was determined to be {-> 3)-beta-D-Glcp-(1 -> 3)-[alpha-D-GlcpA-(1 -> 4)-beta-D-Glcp-(1 -> 6)]-alpha-D-Galp- (1 -> 6)-beta-D-Galp-(1 -> 3)-beta-D-Galp-(1 ->}(n). We demonstrated that 1 mu g/mL CPS could stimulate J774A.1 murine macrophages to release tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) in vitro. Also, we proved that KN2 CPS induced the immune response through Toll-like receptor 4 (TLR4) in the human embryonic kidney (HEK)-293 cells. Strikingly, the hexasaccharide alone shows the same immune response as the CPS, suggesting that the hexasaccharide can shape the adaptive immunity to be a potential vaccine adjuvant. The glucuronic acid (GlcA) on other polysaccharides can affect the immune response, but the GlcA-reduced KN2 CPS and hex-asaccharide still maintain their immunomodulatory activities.
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