Granulibacter bethesdensis, a Pathogen from Patients with Chronic Granulomatous Disease, Produces a Penta-Acylated Hypostimulatory Glycero-D-talo-oct-2-ulosonic Acid-Lipid A Glycolipid (Ko-Lipid A).
Granulibacter bethesdensis, a Pathogen from Patients with Chronic Granulomatous Disease, Produces a Penta-Acylated Hypostimulatory Glycero-D-talo-oct-2-ulosonic Acid-Lipid A Glycolipid (Ko-Lipid A).
复制标题
肉芽肿贝丝斯丁斯是一种来自慢性肉芽肿性疾病患者的病原体，会产生五角囊性的低压测性甘油-D-talo-oct-oct-oct-oct-oct-2-硫酸脂蛋白脂质糖糖（KO-lipid a）。
DOI：
10.3390/ijms22073303
复制
发表时间：
2021-03-24
影响因子：
5.6
通讯作者：
Gallin JI
中科院分区：
文献类型：
--
作者：
Muszyński A;Zarember KA;Heiss C;Shiloach J;Berg LJ;Audley J;Kozyr A;Greenberg DE;Holland SM;Malech HL;Azadi P;Carlson RW;Gallin JI
贝塞登颗粒杆菌可感染慢性肉芽肿病患者，这是一种由吞噬细胞NADPH氧化酶功能降低引起的免疫缺陷。完整的G。Bethesdensis（Gb）与大肠杆菌相比是低刺激性的，即，人类血液中细胞因子的产生需要10 - 100倍的G。bethesdensisCFU/mL比E.杆菌为了更好地了解G. Bethesdensis的脂多糖（GbLPS），并对其脂质A进行了表征。与典型的肠杆菌科不同，假定Gb脂质A从其LPS中释放需要强酸。NMR和质谱证明，分离的糖脂的碳水化合物部分由α-Manp-（1 → 4）-β-GlcpN3N-（1 → 6）-α-GlcpN-（1 → 1）-α-GlcpA四糖组成，其被五个酰基链取代：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。甘油-d-talo-oct-2-ulosonic acid（Ko）作为LPS核心区域的第一组分的鉴定可以解释GbLPS的耐酸性，所述LPS核心区域共价连接至脂质骨架的GlcpN3N。此外，Ko的存在和仅五个酰基链可以解释GbKo-lipidA与E.大肠杆菌脂质A，如通过人血液中的细胞因子诱导所测量的。贝塞登地芽孢杆菌Ko-lipid A糖脂的这些不寻常的结构特性可能有助于发病过程中的免疫逃避和对抗菌肽的抗性。
Granulibacter bethesdensis can infect patients with chronic granulomatous disease, an immunodeficiency caused by reduced phagocyte NADPH oxidase function. Intact G. bethesdensis (Gb) is hypostimulatory compared to Escherichia coli, i.e., cytokine production in human blood requires 10–100 times more G. bethesdensis CFU/mL than E. coli. To better understand the pathogenicity of G. bethesdensis, we isolated its lipopolysaccharide (GbLPS) and characterized its lipid A. Unlike with typical Enterobacteriaceae, 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-Manp-(1→4)-β-GlcpN3N-(1→6)-α-GlcpN-(1⇿1)-α-GlcpA 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 GbLPS. In addition, the presence of Ko and only five acyl chains may explain the >10-fold lower proinflammatory potency of GbKo–lipidA compared to E. coli lipid A, as measured by cytokine induction in human blood. These unusual structural properties of the G.bethesdensis Ko–lipid A glycolipid likely contribute to immune evasion during pathogenesis and resistance to antimicrobial peptides.
登录
查看更多内容
影响因子：
7.3
作者：
Matsuura M
通讯作者：
Matsuura M
影响因子：
6.7
作者：
Greenberg, David E.;Ding, Li;Holland, Steven M.
通讯作者：
Holland, Steven M.
影响因子：
4.3
作者：
Brown, Dusty B.;Muszynski, Artur;Carlson, Russell W.
通讯作者：
Carlson, Russell W.
影响因子：
2.1
作者：
Bera, R;Nayak, A;Bhadra, R
通讯作者：
Bhadra, R
影响因子：
3.1
作者：
Chu, Jessica;Smelkinson, Margery G.;Gallin, John I.
通讯作者：
Gallin, John I.