经蜱叮咬的转染功能互补的传播相关蛋白可恢复螺旋体的感染力。
Transgenic functional complementation with a transmission -associated protein restores spirochete infectivity by tick bite.
机构信息
Laboratory of Zoonotic Pathogens, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 903 South 4th Street, Hamilton, MT, 59840, USA.
Laboratory of Zoonotic Pathogens, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 903 South 4th Street, Hamilton, MT, 59840, USA.
出版信息
Ticks Tick Borne Dis. 2020 May;11(3):101377. doi: 10.1016/j.ttbdis.2020.101377. Epub 2020 Jan 20.
The relapsing fever spirochete Borrelia hermsii and the Lyme disease spirochete Borrelia burgdorferi sensu stricto each produces an abundant, orthologous, outer membrane protein, Vtp and OspC, respectively, when transmitted by tick bite. Gene inactivation studies have shown that both proteins are essential for spirochete infectivity when transmitted by their respective tick vectors. Therefore, we transformed a vtp-minus mutant of B. hermsii with ospC from B. burgdorferi and examined the behavior of this transgenic spirochete in its soft tick vector Ornithodoros hermsi. IFA staining indicated up to 97.8 % of the transgenic B. hermsii upregulated OspC in the ticks' salivary glands compared to no more than 12.8 % in the midgut, similar to our previous findings with wild-type B. hermsii producing Vtp. Transformation with ospC also restored B. hermsii infectivity to mice when fed upon by infected ticks. Previous sequence analysis of Vtp for 79 isolates and DNA samples of B. hermsii in our laboratory showed this protein is highly polymorphic with 9 divergent amino acid types, yet strikingly the signal peptide is identical among all samples and the same for all OspC signal peptides for B. burgdorferi and related species examined to date. Searches in multiple genome sequences for other species of relapsing fever spirochetes failed to find the same signal peptide sequence to help identify potential transmission-associated proteins. However, some candidate signal peptides with highly similar sequences were found and worthy of future efforts with other species. While OspC of B. burgdorferi restored infectivity to a Vtp-minus mutant of B. hermsii, the functions of these proteins are not known. Our results should stimulate investigators to search for orthologous transmission-associated proteins in other tick-borne spirochetes to better understand how this group of pathogens has coevolved with diverse tick vectors.
回归热螺旋体伯氏疏螺旋体和莱姆病螺旋体伯氏疏螺旋体严格意义上分别产生大量的、同源的外膜蛋白 Vtp 和 OspC，当通过蜱叮咬传播时。基因失活研究表明，当通过各自的蜱载体传播时，这两种蛋白质对于螺旋体的感染力都是必不可少的。因此，我们用伯氏疏螺旋体的 ospC 转化了 vtp 缺失突变的 B. hermsii，并在其软蜱载体 Ornithodoros hermsi 中研究了这种转基因螺旋体的行为。IFA 染色表明，与在中肠中不超过 12.8%的情况相比，多达 97.8%的转基因 B. hermsii 在蜱的唾液腺中上调了 OspC，与我们之前用产生 Vtp 的野生型 B. hermsii 所做的发现相似。当用感染的蜱喂食时，ospC 的转化也恢复了 B. hermsii 对小鼠的感染力。先前对我们实验室中 79 个分离株和 B. hermsii 的 Vtp 进行的序列分析表明，这种蛋白质高度多态，有 9 种不同的氨基酸类型，但令人惊讶的是，所有样本中的信号肽都是相同的，与迄今为止检查的所有伯氏疏螺旋体和相关物种的 OspC 信号肽相同。在多个基因组序列中搜索其他回归热螺旋体物种未能找到相同的信号肽序列来帮助识别潜在的与传播相关的蛋白质。然而，发现了一些具有高度相似序列的候选信号肽，值得在其他物种中进一步研究。虽然 B. burgdorferi 的 OspC 恢复了 B. hermsii vtp 缺失突变体的感染力，但这些蛋白质的功能尚不清楚。我们的研究结果应该会激发研究人员在其他蜱传螺旋体中寻找同源的传播相关蛋白，以更好地了解这组病原体是如何与不同的蜱载体共同进化的。
Zotero 插件