Department of Microbiology and Physiological Systems, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, MA 01655, USA.
Infect Immun. 2011 Sep;79(9):3501-9. doi: 10.1128/IAI.00163-11. Epub 2011 Jun 27.
After transmission by an infected tick, the Lyme disease spirochete, Borrelia burgdorferi sensu lato, colonizes the mammalian skin and may disseminate systemically. The three major species of Lyme disease spirochete--B. burgdorferi sensu stricto, B. garinii, and B. afzelii--are associated with different chronic disease manifestations. Colonization is likely promoted by the ability to bind to target tissues, and Lyme disease spirochetes utilize multiple adhesive molecules to interact with diverse mammalian components. The allelic variable surface lipoprotein decorin binding protein A (DbpA) promotes bacterial binding to the proteoglycan decorin and to the glycosaminoglycan (GAG) dermatan sulfate. To assess allelic variation of DbpA in GAG-, decorin-, and cell-binding activities, we expressed dbpA alleles derived from diverse Lyme disease spirochetes in B. burgdorferi strain B314, a noninfectious and nonadherent strain that lacks dbpA. Each DbpA allele conferred upon B. burgdorferi strain B314 the ability to bind to cultured kidney epithelial (but not glial or endothelial) cells, as well as to purified decorin and dermatan sulfate. Nevertheless, allelic variation of DbpA was associated with dramatic differences in substrate binding activity. In most cases, decorin and dermatan sulfate binding correlated well, but DbpA of B. afzelii strain VS461 promoted differential binding to decorin and dermatan sulfate, indicating that the two activities are separable. DbpA from a clone of B. burgdorferi strain N40 that can cause disseminated infection in mice displayed relatively low adhesive activity, indicating that robust DbpA-mediated adhesive activity is not required for spread in the mammalian host.
经感染蜱传播后，莱姆病螺旋体，即伯氏疏螺旋体，定植于哺乳动物皮肤并可能全身传播。三种主要的莱姆病螺旋体——伯氏疏螺旋体、伽氏疏螺旋体和阿费尔森疏螺旋体——与不同的慢性疾病表现相关。定植可能是由结合靶组织的能力所促进的，莱姆病螺旋体利用多种黏附分子与多种哺乳动物成分相互作用。等位基因可变表面脂蛋白聚糖结合蛋白 A（DbpA）促进细菌与蛋白聚糖核心蛋白聚糖和糖胺聚糖（GAG）硫酸皮肤素结合。为了评估 GAG、核心蛋白聚糖和细胞结合活性中 DbpA 的等位基因变异，我们在伯氏疏螺旋体 B314 中表达了来自不同莱姆病螺旋体的 dbpA 等位基因，B314 是一种无传染性和无黏附性的菌株，缺乏 dbpA。每个 DbpA 等位基因赋予伯氏疏螺旋体 B314 与培养的肾脏上皮（而非神经胶质或内皮）细胞结合的能力，以及与纯化的核心蛋白聚糖和硫酸皮肤素结合的能力。然而，DbpA 的等位基因变异与底物结合活性的显著差异相关。在大多数情况下，核心蛋白聚糖和硫酸皮肤素结合良好，但 B. afzelii 菌株 VS461 的 DbpA 促进了对核心蛋白聚糖和硫酸皮肤素的差异结合，表明这两种活性是可分离的。来自能够在小鼠中引起全身性感染的伯氏疏螺旋体 N40 克隆的 DbpA 表现出相对较低的黏附活性，表明强大的 DbpA 介导的黏附活性不是在哺乳动物宿主中传播所必需的。
