Lyme disease, also known as Lyme borreliosis, is the most common tick-transmitted disease in the Northern Hemisphere. The disease is caused by the bacterial spirochete Borrelia burgdorferi and other related Borrelia species. One of the many fascinating features of this unique pathogen is an elaborate system for antigenic variation, whereby the sequence of the surface-bound lipoprotein VlsE is continually modified through segmental gene conversion events. This perpetual changing of the guard allows the pathogen to remain one step ahead of the acquired immune response, enabling persistent infection. Accordingly, the vls locus is the most evolutionarily diverse genetic element in Lyme disease-causing borreliae. Small stretches of information are transferred from a series of silent cassettes in the vls locus to generate an expressed mosaic vlsE gene version that contains genetic information from several different silent cassettes, resulting in ∼1040 possible vlsE sequences. Yet, despite its extreme evolutionary flexibility, the locus has rigidly conserved structural features. These include a telomeric location of the vlsE gene, an inverse orientation of vlsE and the silent cassettes, the presence of nearly perfect inverted repeats of ∼100 bp near the 5' end of vlsE, and an exceedingly high concentration of G runs in vlsE and the silent cassettes. We discuss the possible roles of these evolutionarily conserved features, highlight recent findings from several studies that have used next-generation DNA sequencing to unravel the switching process, and review advances in the development of a mini-vls system for genetic manipulation of the locus.

中文翻译：

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卫兵换岗：莱姆病螺旋体如何破坏宿主免疫反应。


莱姆病，也称为莱姆疏螺旋体病，是北半球最常见的蜱传播疾病。该疾病是由细菌螺旋体伯氏疏螺旋体和其他相关疏螺旋体物种引起的。这种独特病原体的许多迷人特征之一是复杂的抗原变异系统，表面结合脂蛋白 VlsE 的序列通过分段基因转换事件不断修改。这种不断变化的守卫使得病原体能够比获得性免疫反应领先一步，从而实现持续感染。因此，vls 基因座是引起莱姆病的疏螺旋体中最具进化多样性的遗传元件。小段信息从 vls 基因座中的一系列沉默盒转移，生成表达的镶嵌 vlsE 基因版本，其中包含来自几个不同沉默盒的遗传信息，从而产生约 1040 个可能的 vlsE 序列。然而，尽管该基因座具有极高的进化灵活性，但其结构特征却严格保守。其中包括 vlsE 基因的端粒位置、vlsE 和沉默盒的反向方向、vlsE 5' 端附近近乎完美的约 100 bp 反向重复的存在，以及 vlsE 和 vlsE 中极高浓度的 G 运行。无声的磁带。我们讨论了这些进化上保守的特征的可能作用，重点介绍了几项使用下一代 DNA 测序来揭示转换过程的研究的最新发现，并回顾了用于基因座遗传操作的 mini-vls 系统的开发进展。