Leong J M, Wang H, Magoun L, Field J A, Morrissey P E, Robbins D, Tatro J B, Coburn J, Parveen N
Department of Molecular Genetics and Microbiology, University of Massachusetts Medical Center, Worcester 01655, USA.
Infect Immun. 1998 Mar;66(3):994-9. doi: 10.1128/IAI.66.3.994-999.1998.
The Lyme disease spirochete, Borrelia burgdorferi, infects multiple tissues, such as the heart, joint, skin, and nervous system and has been shown to recognize heparan sulfate and dermatan sulfate proteoglycans. In this study, we examined the contribution of different classes of proteoglycans to the attachment of the infectious B. burgdorferi strain N40 to several immortalized cell lines and primary cultured cells, including endothelial cells and brain cells. Bacterial attachment was inhibited by exogenous proteoglycans or by treatment of host cells with inhibitors of proteoglycan synthesis or sulfation, indicating that proteoglycans play a critical role in bacterial binding to diverse cell types. Binding to primary bovine capillary endothelial cells or a human endothelial cell line was also inhibited by digestion with heparinase or heparitinase but not with chondroitinase ABC. In contrast, binding to glial cell-enriched brain cell cultures or to a neuronal cell line was inhibited by all three lyases. Binding of strain N40 to immobilized heparin could be completely inhibited by dermatan sulfate, and conversely, binding to dermatan sulfate could be completely blocked by heparin. As measured by 50% inhibitory dose, heparin was a better inhibitor of binding than dermatan sulfate, regardless of whether the substrate was heparin or dermatan sulfate. These results are consistent with the hypotheses that the species of proteoglycans recognized by B. burgdorferi vary with cell type and that bacterial recognition of different proteoglycans is mediated by the same bacterial molecule(s).
莱姆病螺旋体，伯氏疏螺旋体，可感染多种组织，如心脏、关节、皮肤和神经系统，并且已证明它能识别硫酸乙酰肝素和硫酸皮肤素蛋白聚糖。在本研究中，我们检测了不同种类的蛋白聚糖对感染性伯氏疏螺旋体菌株N40附着于几种永生化细胞系和原代培养细胞（包括内皮细胞和脑细胞）的作用。外源性蛋白聚糖或用蛋白聚糖合成或硫酸化抑制剂处理宿主细胞可抑制细菌附着，这表明蛋白聚糖在细菌与多种细胞类型的结合中起关键作用。用肝素酶或类肝素酶消化可抑制与原代牛毛细血管内皮细胞或人内皮细胞系的结合，但用软骨素酶ABC消化则无此作用。相反，所有这三种裂解酶均可抑制与富含胶质细胞的脑细胞培养物或神经元细胞系的结合。菌株N40与固定化肝素的结合可被硫酸皮肤素完全抑制，反之，与硫酸皮肤素的结合可被肝素完全阻断。通过50%抑制剂量测定，无论底物是肝素还是硫酸皮肤素，肝素都是比硫酸皮肤素更好的结合抑制剂。这些结果与以下假设一致：伯氏疏螺旋体识别的蛋白聚糖种类因细胞类型而异，并且细菌对不同蛋白聚糖的识别是由相同的细菌分子介导的。
