Identification of Borrelia burgdorferi outer surface proteins
Identification of Borrelia burgdorferi outer surface proteins
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DOI：
10.1128/iai.74.1.296-304.2006
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发表时间：
2006-01-01
影响因子：
3.1
通讯作者：
Akins, DR
中科院分区：
文献类型：
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作者：
Brooks, CS;Vuppala, SR;Akins, DR
在过去的十年中，已经发现了几种伯氏疏螺旋体外表面蛋白，在这种螺旋体从扁虱传播到哺乳动物的过程中，它们受到温度和/或哺乳动物宿主特异性信号的上调。鉴于这些差异上调的蛋白可能在伯氏杆菌传播和莱姆病发病机制中发挥的潜在作用(S)，最近人们非常关注识别更多的贝氏杆菌外表面蛋白。为了鉴定未鉴定的伯氏杆菌外表面蛋白，我们先前对温移和哺乳动物适应宿主的伯氏杆菌进行了全面的基因表达谱分析。联合微阵列分析显示，许多编码已知和可能的外表面蛋白的基因在哺乳动物宿主适应的伯氏杆菌中下调。然而，与此同时，在传播和感染过程中，几个编码可能的外表面蛋白的不同基因被发现上调。在已鉴定的外表面蛋白中，生化和表面定位分析证实有7个蛋白(Bb0405、Bb0689、BbA36、BbA64、BbA66、BbA69和Bb142)定位于伯氏杆菌的表面。此外，使用扁虱感染的狒狒的血清进行的酶联免疫吸附分析表明，所有被鉴定的七种外表面蛋白都是免疫原性的，并且在自然感染期间都会产生针对所有七种蛋白的抗体。针对所有七种表面蛋白产生的特异性抗体被发现对伯氏杆菌具有杀菌作用，表明这些新鉴定的外表面蛋白是分析第二代莱姆病疫苗原的主要候选者。
Several Borrelia burgdorferi outer surface proteins have been identified over the past decade that are up-regulated by temperature- and/or mammalian host-specific signals as this spirochete is transmitted from ticks to mammals. Given the potential role(s) that these differentially up-regulated proteins may play in B. burgdorferi transmission and Lyme disease pathogenesis, much attention has recently been placed on identifying additional borrelial outer surface proteins. To identify uncharacterized B. burgdorferi outer surface proteins, we previously performed a comprehensive gene expression profiling analysis of temperature-shifted and mammalian host-adapted B. burgdorferi. The combined microarray analyses revealed that many genes encoding known and putative outer surface proteins are down-regulated in mammalian host-adapted B. burgdorferi. At the same time, however, several different genes encoding putative outer surface proteins were found to be up-regulated during the transmission and infection process. Among the putative outer surface proteins identified, biochemical and surface localization analyses confirmed that seven (Bb0405, Bb0689, BbA36, BbA64, BbA66, BbA69, and Bb142) are localized to the surface of B. burgdorferi. Furthermore, enzyme-linked immunosorbent assay analysis using serum from tick-infested baboons indicated that all seven outer surface proteins identified are immunogenic and that antibodies are generated against all seven during a natural infection. Specific antibodies generated against all seven of these surface proteins were found to be bactericidal against B. burgdorferi, indicating that these newly identified outer surface proteins are prime candidates for analysis as second-generation Lyme disease vaccinogens.