Department of Microbiology and Molecular Genetics, University of California, Irvine, Irvine, California, USA.
Infect Immun. 2012 May;80(5):1881-90. doi: 10.1128/IAI.06419-11. Epub 2012 Feb 21.
Borrelia hermsii and other relapsing fever (RF) species are noted for their highly polymorphic surface antigens, the variable major proteins (VMP). Less is known about other surface proteins of these pathogens in either their vertebrate reservoirs or arthropod vectors. To further characterize these proteins, we elicited antibodies against VMP-less cells, noted antibody reactions against whole cells and cell components, and then subjected selected antigens to mass spectroscopy for amino acid sequencing for comparison against a B. hermsii genome database. One of the derived monoclonal antibodies, H0120, agglutinated spirochetes, and in Western blot analyses, it bound to a 14-kDa protein of whole cells and their membrane fractions but not after protease treatment. A search of open reading frames of the B. hermsii genome with extracted peptides identified the 14-kDa protein with bha128, a 453-nucleotide gene of the 175-kb linear plasmid. The bha128 gene was synthesized and expressed in Escherichia coli. The protein product was bound by antibody H0120. Genes homologous to bha128 occur in the RF species Borrelia turicatae, B. duttonii, and B. recurrentis but not in Lyme disease Borrelia species or other organisms. The following findings indicated an association of BHA128, renamed Alp, with the tick environment: (i) Alp was produced at higher levels at 23°C than at 34 °C; (ii) almost all spirochetes in tick salivary glands were bound by the H0120 antibody, but only ~1% of spirochetes in the blood of infected mice were bound; and (iii) infected mice produced antibodies to several B. hermsii antigens but not detectably to native or recombinant Alp.
伯氏疏螺旋体和其他回归热(RF)物种以其高度多态的表面抗原,即可变主要蛋白(VMP)而闻名。关于这些病原体在脊椎动物宿主或节肢动物载体中的其他表面蛋白,人们知之甚少。为了进一步描述这些蛋白质,我们针对缺乏 VMP 的细胞产生了抗体,注意到针对整个细胞和细胞成分的抗体反应,然后对选定的抗原进行质谱分析,以与伯氏疏螺旋体基因组数据库进行比较。从衍生的单克隆抗体之一 H0120 中,它可以凝集螺旋体,在 Western blot 分析中,它与整个细胞及其膜部分的 14 kDa 蛋白结合,但在蛋白酶处理后不结合。使用提取的肽对伯氏疏螺旋体基因组的开放阅读框进行搜索,鉴定出 14 kDa 蛋白与 bha128 相关,bha128 是 175kb 线性质粒的 453 个核苷酸基因。bha128 基因在大肠杆菌中合成并表达。蛋白产物被抗体 H0120 结合。与 RF 物种伯氏疏螺旋体、B. duttonii 和 B. recurrentis 同源的基因,但与莱姆病伯氏疏螺旋体或其他生物体不同。以下发现表明 BHA128(更名为 Alp)与蜱环境有关:(i)Alp 在 23°C 时的产量高于 34°C;(ii)在感染蜱的唾液腺中的几乎所有螺旋体都被 H0120 抗体结合,但在感染小鼠的血液中只有约 1%的螺旋体被结合;(iii)感染小鼠产生针对几种伯氏疏螺旋体抗原的抗体,但不能检测到针对天然或重组 Alp 的抗体。