Garton Natalie J, Gilleron Martine, Brando Thérèse, Dan Han-Hong, Giguère Steeve, Puzo Germain, Prescott John F, Sutcliffe Iain C
Institute of Pharmacy, Chemistry and Biomedical Sciences, the University of Sunderland, Sunderland SR2 3SD, United Kingdom.
J Biol Chem. 2002 Aug 30;277(35):31722-33. doi: 10.1074/jbc.M203008200. Epub 2002 Jun 18.
Rhodococcus equi is a major cause of foal morbidity and mortality. We have investigated the presence of lipoglycan in this organism as closely related bacteria, notably Mycobacterium tuberculosis, produce lipoarabinomannans (LAM) that may play multiple roles as virulence determinants. The lipoglycan was structurally characterized by gas chromatography-mass spectrometry following permethylation, capillary electrophoresis after chemical degradation, and (1)H and (31)P and two-dimensional heteronuclear nuclear magnetic resonance studies. Key structural features of the lipoglycan are a linear alpha-1,6-mannan with side chains containing one 2-linked alpha-d-Manp residue. This polysaccharidic backbone is linked to a phosphatidylinositol mannosyl anchor. In contrast to mycobacterial LAM, there are no extensive arabinan domains but single terminal alpha-d-Araf residue capping the 2-linked alpha-d-Manp. The lipoglycan binds concanavalin A and mannose-binding protein consistent with the presence of t-alpha-d-Manp residues. We studied the ability of the lipoglycans to induce cytokines from equine macrophages, in comparison to whole cells of R. equi. These data revealed patterns of cytokine mRNA induction that suggest that the lipoglycan is involved in much of the early macrophage cytokine response to R. equi infection. These studies identify a novel LAM variant that may contribute to the pathogenesis of disease caused by R. equi.
马红球菌是幼驹发病和死亡的主要原因。我们研究了这种微生物中脂多糖的存在情况，因为密切相关的细菌，尤其是结核分枝杆菌，会产生脂阿拉伯甘露聚糖（LAM），其可能作为毒力决定因素发挥多种作用。通过甲基化后的气相色谱 - 质谱、化学降解后的毛细管电泳以及（1）H、（31）P和二维异核核磁共振研究对脂多糖进行了结构表征。脂多糖的关键结构特征是具有线性α-1,6-甘露聚糖，其侧链含有一个2-连接的α-d-Manp残基。这种多糖主链与磷脂酰肌醇甘露糖基锚相连。与分枝杆菌LAM不同，不存在广泛的阿拉伯聚糖结构域，而是单个末端α-d-Araf残基封端2-连接的α-d-Manp。脂多糖与伴刀豆球蛋白A和甘露糖结合蛋白结合，这与t-α-d-Manp残基的存在一致。与马红球菌全细胞相比，我们研究了脂多糖诱导马巨噬细胞产生细胞因子的能力。这些数据揭示了细胞因子mRNA诱导模式，表明脂多糖参与了巨噬细胞对马红球菌感染的许多早期细胞因子反应。这些研究鉴定出一种新型LAM变体，其可能促成马红球菌引起的疾病发病机制。
