Lin Yi-Pin, Bhowmick Rudra, Coburn Jenifer, Leong John M
Department of Molecular Biology and Microbiology, Tufts University School of Medicine, 136 Harrison Ave, Boston, MA, 02111, USA.
Division of Infectious Disease, Center for Infectious Disease Research, Medical College of Wisconsin, 8701 Watertown Plank Rd., Milwaukee, WI, 53226, USA.
Cell Microbiol. 2015 Oct;17(10):1464-76. doi: 10.1111/cmi.12448. Epub 2015 May 13.
Borrelia burgdorferi, the agent of Lyme disease, spreads from the site of the tick bite to tissues such as heart, joints and the nervous tissues. Host glycosaminoglycans, highly modified repeating disaccharides that are present on cell surfaces and in extracellular matrix, are common targets of microbial pathogens during tissue colonization. While several dermatan sulfate-binding B. burgdorferi adhesins have been identified, B. burgdorferi adhesins documented to promote spirochetal binding to heparan sulfate have not yet been identified. OspEF-related proteins (Erps), a large family of plasmid-encoded surface lipoproteins that are produced in the mammalian host, can be divided into the OspF-related, OspEF-leader peptide (Elp) and OspE-related subfamilies. We show here that a member of the OspF-related subfamily, ErpG, binds to heparan sulfate and when produced on the surface of an otherwise non-adherent B. burgdorferi strain, ErpG promotes heparan sulfate-mediated bacterial attachment to the glial but not the endothelial, synovial or respiratory epithelial cells. Six other OspF-related proteins were capable of binding heparan sulfate, whereas representative OspE-related and Elp proteins lacked this activity. These results indicate that OspF-related proteins are heparan sulfate-binding adhesins, at least one of which promotes bacterial attachment to glial cells.
莱姆病的病原体伯氏疏螺旋体从蜱叮咬部位扩散到心脏、关节和神经组织等组织。宿主糖胺聚糖是存在于细胞表面和细胞外基质中的高度修饰的重复二糖，是微生物病原体在组织定植过程中的常见靶点。虽然已经鉴定出几种与硫酸皮肤素结合的伯氏疏螺旋体粘附素，但尚未鉴定出能促进螺旋体与硫酸乙酰肝素结合的伯氏疏螺旋体粘附素。OspEF相关蛋白（Erps）是在哺乳动物宿主中产生的一大类质粒编码的表面脂蛋白，可分为OspF相关、OspEF前导肽（Elp）和OspE相关亚家族。我们在此表明，OspF相关亚家族的成员ErpG与硫酸乙酰肝素结合，并且当在原本不粘附的伯氏疏螺旋体菌株表面产生时，ErpG促进硫酸乙酰肝素介导的细菌附着于神经胶质细胞而非内皮细胞、滑膜细胞或呼吸道上皮细胞。其他六种OspF相关蛋白能够结合硫酸乙酰肝素，而代表性的OspE相关蛋白和Elp蛋白缺乏这种活性。这些结果表明，OspF相关蛋白是硫酸乙酰肝素结合粘附素，其中至少一种促进细菌附着于神经胶质细胞。
