Division of Infectious Disease, Wadsworth Center, New York State Department of Health, Albany, New York, USA.
New York Structural Biology Centergrid.422632.3, New York, New York, USA.
mSphere. 2022 Aug 31;7(4):e0025222. doi: 10.1128/msphere.00252-22. Epub 2022 Jul 25.
Decorin binding protein A (DbpA) is a surface adhesin of Borrelia burgdorferi, the causative agent of Lyme disease. While DbpA is one of the most immunogenic of B. burgdorferi's nearly 100 lipoproteins, the B cell epitopes on DbpA recognized by humans following B. burgdorferi infection have not been fully elucidated. In this report we profiled ~270 B. burgdorferi-seropositive human serum samples for IgM and IgG reactivity with a tiled DbpA 18-mer peptide array derived from B. burgdorferi strains B31 and 297. Using enzyme-linked immunosorbent assays (ELISA) and multiplex immunoassays (MIA), we identified 12 DbpA-derived peptides whose antibody reactivities were significantly elevated (generally <10-fold) in B. burgdorferi-seropositive sera, compared to those measured in a healthy cohort. The most reactive peptide (>80-fold IgG, 10-fold IgM) corresponded to residues 64 to 81, which map to an exposed flexible loop between DbpA's α-helix 1 and α-helix 2. This loop, whose sequence is identical between strains B31 and 297, overhangs DbpA's substrate binding pocket. A second strongly reactive antibody target (>80-fold IgG, 3 to 5-fold IgM) mapped to DbpA's C-terminus, a lysine rich tail implicated in attachment to glycosaminoglycans. We postulate that antibody responses against these two targets on DbpA could limit B.burgdorferi's ability to attach to and colonize distal tissues during the early stages of infection. The bacterium, Borrelia burgdorferi, is the causative agent of Lyme disease, the most reported tick-borne illness in the United States. In humans, clinical manifestations of Lyme disease are complex and can persist for months, even in the face of a robust antibody response directed against numerous B. burgdorferi surface proteins, including decorin binding protein A (DbpA), which is involved in the early stages of infection. In this study we employed ~270 serum samples from B. burgdorferi-seropositive individuals to better understand human antibody reactivity to specific regions (called epitopes) of DbpA and how such antibodies may function in limiting B. burgdorferi dissemination and tissue colonization.
DbpA 结合蛋白 A（DbpA）是伯氏疏螺旋体的表面黏附素，伯氏疏螺旋体是莱姆病的病原体。尽管 DbpA 是伯氏疏螺旋体近 100 种脂蛋白中最具免疫原性的一种，但人类在感染伯氏疏螺旋体后识别的 DbpA B 细胞表位尚未完全阐明。在本报告中，我们对约 270 份伯氏疏螺旋体血清阳性的人类血清样本进行了分析，这些样本与源自伯氏疏螺旋体菌株 B31 和 297 的平铺 DbpA 18 肽阵列发生 IgM 和 IgG 反应。使用酶联免疫吸附测定（ELISA）和多重免疫测定（MIA），我们鉴定出 12 个 DbpA 衍生肽，与健康队列相比，这些肽在伯氏疏螺旋体血清阳性样本中的抗体反应显著升高（通常为<10 倍）。最具反应性的肽（>80 倍 IgG，10 倍 IgM）对应于 64 至 81 位残基，这些残基位于 DbpA 的α-螺旋 1 和α-螺旋 2 之间的一个暴露的柔性环上。该环在 B31 和 297 菌株之间序列相同，悬垂于 DbpA 的底物结合口袋上方。第二个强烈反应的抗体靶标（>80 倍 IgG，3 至 5 倍 IgM）映射到 DbpA 的 C 末端，富含赖氨酸的尾部与糖胺聚糖的附着有关。我们推测，针对 DbpA 上这两个靶标的抗体反应可能会限制伯氏疏螺旋体在感染早期附着和定殖远端组织的能力。这种细菌，伯氏疏螺旋体，是莱姆病的病原体，是美国报告最多的蜱传疾病。在人类中，莱姆病的临床表现复杂，即使针对许多伯氏疏螺旋体表面蛋白产生了强大的抗体反应，包括参与感染早期阶段的细胞外基质结合蛋白 A（DbpA），也可能持续数月。在这项研究中，我们使用了约 270 份来自伯氏疏螺旋体血清阳性个体的血清样本，以更好地了解人类针对 DbpA 特定区域（称为表位）的抗体反应，以及这些抗体如何在限制伯氏疏螺旋体的传播和组织定植方面发挥作用。
