A small intergenic region of lp17 is required for evasion of adaptive immunity and induction of pathology by the Lyme disease spirochete
A small intergenic region of lp17 is required for evasion of adaptive immunity and induction of pathology by the Lyme disease spirochete
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DOI：
10.1111/cmi.13029
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发表时间：
2019-07-01
影响因子：
3.4
通讯作者：
Bankhead, Troy
中科院分区：
文献类型：
--
作者：
Casselli, Timothy;Crowley, Michael A.;Bankhead, Troy
莱姆病的病原体伯氏疏螺旋体（Borrelia burgdorferi）具有单个线性染色体和23个以上线性和环状质粒。只有少数这些质粒，包括线性质粒17，在延长的体外传代过程中保持接近绝对的保真度，并且它们编码的任何推定的毒力决定簇的表征最近才开始。在这项工作中，缺乏一个4.7 kb片段的lp17突变体进行了研究。这种lp17突变体在小鼠组织中的定殖显著受损，诱导心脏炎和关节炎的能力也是如此。在严重的联合免疫缺陷（SCID）小鼠的组织定植的缺陷得到缓解，暗示了该质粒区域在适应性免疫逃避中的作用。通过遗传互补，突变表型可以完全归因于一个317 bp的基因间区域，对应于中断的bbd07 ORF和上游序列。基因间区域被发现是转录活性的，和突变体螺旋体缺乏这个区域表现出整体差异的抗原谱在感染的免疫活性鼠宿主。总体而言，这项研究是第一个提供证据的lp17参与殖民的关节和心脏组织，沿着相关的病理引起的莱姆病螺旋体。
The causative agent of Lyme disease, Borrelia burgdorferi, harbours a single linear chromosome and upwards of 23 linear and circular plasmids. Only a minority of these plasmids, including linear plasmid 17, are maintained with near-absolute fidelity during extended in vitro passage, and characterisation of any putative virulence determinants they encode has only recently begun. In this work, a mutant lacking a 4.7 kb fragment of lp17 was studied. Colonisation of murine tissues by this lp17 mutant was significantly impaired, as was the ability to induce carditis and arthritis. The deficiency in tissue colonisation was alleviated in severe combined immunodeficient (SCID) mice, implicating a role for this plasmid region in adaptive immune evasion. Through genetic complementation, the mutant phenotype could be fully attributed to a 317 bp intergenic region that corresponds to the discontinued bbd07 ORF and upstream sequence. The intergenic region was found to be transcriptionally active, and mutant spirochetes lacking this region exhibited an overall difference in the antigenic profile during infection of an immunocompetent murine host. Overall, this study is the first to provide evidence for the involvement of lp17 in colonisation of joint and heart tissues, along with the associated pathologies caused by the Lyme disease spirochete.