Complex Carbohydrate Research Center, University of Georgia, Athens, GA 30602, USA.
Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Int J Mol Sci. 2021 Mar 24;22(7):3303. doi: 10.3390/ijms22073303.
can infect patients with chronic granulomatous disease, an immunodeficiency caused by reduced phagocyte NADPH oxidase function. Intact () is hypostimulatory compared to , i.e., cytokine production in human blood requires 10-100 times more CFU/mL than . To better understand the pathogenicity of , we isolated its lipopolysaccharide (LPS) and characterized its lipid A. Unlike with typical , the release of presumptive Gb lipid A from its LPS required a strong acid. NMR and mass spectrometry demonstrated that the carbohydrate portion of the isolated glycolipid consists of α-Man-(1→4)-β-GlcN3N-(1→6)-α-GlcN-(1⇿1)-α-GlcA tetra-saccharide substituted with five acyl chains: the amide-linked N-3' 14:0(3-OH), N-2' 16:0(3-O16:0), and N-2 18:0(3-OH) and the ester-linked O-3 14:0(3-OH) and 16:0. The identification of glycero-d-talo-oct-2-ulosonic acid (Ko) as the first constituent of the core region of the LPS that is covalently attached to GlcpN3N of the lipid backbone may account for the acid resistance of LPS. In addition, the presence of Ko and only five acyl chains may explain the >10-fold lower proinflammatory potency of Ko-lipidA compared to lipid A, as measured by cytokine induction in human blood. These unusual structural properties of the Ko-lipid A glycolipid likely contribute to immune evasion during pathogenesis and resistance to antimicrobial peptides.
可以感染患有慢性肉芽肿病的患者，这是一种吞噬细胞 NADPH 氧化酶功能降低引起的免疫缺陷。完整的 () 与相比是低刺激的，即人类血液中的细胞因子产生需要比 多 10-100 倍的 CFU/mL。为了更好地理解 的致病性，我们分离了它的脂多糖 (LPS) 并对其脂质 A 进行了表征。与典型的 LPS 不同，从 LPS 中释放假定的 Gb 脂质 A 需要强酸。NMR 和质谱证明，分离的糖脂的碳水化合物部分由 α-Man-(1→4)-β-GlcN3N-(1→6)-α-GlcN-(1⇿1)-α-GlcA 四糖组成，取代了五个酰基链：酰胺连接的 N-3' 14:0(3-OH)、N-2' 16:0(3-O16:0)和 N-2 18:0(3-OH)以及酯连接的 O-3 14:0(3-OH)和 16:0。鉴定甘油-d-塔洛-oct-2-ulosonic 酸 (Ko) 为 LPS 共价连接到脂质主链的 GlcpN3N 的核心区域的第一个成分，可能解释了 LPS 的耐酸性。此外，Ko 和仅五个酰基链的存在可能解释了 Ko-脂质 A 与 脂质 A 相比，促炎效力低 10 倍以上，如人血中细胞因子诱导所测量的。这种 Ko-脂质 A 糖脂的不寻常结构特性可能有助于在发病机制期间逃避免疫和抵抗抗菌肽。
