High-throughput nanopore sequencing of Treponema pallidum tandem repeat genes arp and tp0470 reveals clade-specific patterns and recapitulates global whole genome phylogeny.
High-throughput nanopore sequencing of Treponema pallidum tandem repeat genes arp and tp0470 reveals clade-specific patterns and recapitulates global whole genome phylogeny.
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DOI：
10.3389/fmicb.2022.1007056
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发表时间：
2022
影响因子：
5.2
通讯作者：
Greninger, Alexander L.
中科院分区：
文献类型：
--
作者：
Lieberman, Nicole A. P.;Armstrong, Thaddeus D.;Chung, Benjamin;Pfalmer, Daniel;Hennelly, Christopher M.;Haynes, Austin;Romeis, Emily;Wang, Qian-Qiu;Zhang, Rui-Li;Kou, Cai-Xia;Ciccarese, Giulia;Dal Conte, Ivano;Cusini, Marco;Drago, Francesco;Nakayama, Shu-ichi;Lee, Kenichi;Ohnishi, Makoto;Konda, Kelika A.;Vargas, Silver K.;Eguiluz, Maria;Caceres, Carlos F.;Klausner, Jeffrey D.;Mitja, Oriol;Rompalo, Anne;Mulcahy, Fiona;Hook, Edward W.;Hoffman, Irving F.;Matoga, Mitch M.;Zheng, Heping;Yang, Bin;Lopez-Medina, Eduardo;Ramirez, Lady G.;Radolf, Justin D.;Hawley, Kelly L.;Salazar, Juan C.;Lukehart, Sheila A.;Sena, Arlene C.;Parr, Jonathan B.;Giacani, Lorenzo;Greninger, Alexander L.
关键词：
大多数梅毒螺旋体基因组的测序排除了编码酸性重复蛋白（阿普）的tp0470和tp0433基因中的重复区域。作为了解这些基因及其编码蛋白质的进化和功能的第一步，我们开发了一个方案，从六大洲10个国家收集的212个临床样本中对tp0470和阿普基因进行纳米孔测序。tp0470和阿普重复结构都概括了整个基因组的进化史，并出现了亚进化枝特异性模式。tp0470重复序列的数目平均看来在Nichols样进化枝菌株中比在SS14样进化枝菌株中高。与以前的研究一致，我们发现，14-重复阿普序列占主导地位，在两个主要的分支，但组合和重复类型的顺序不同的亚分支，与许多阿普序列变异限于一个单一的亚分支。虽然通过全基因组测序紧密相关的菌株通常具有相同的阿普重复长度，但情况并非总是如此。TP 0470的结构建模表明，8个残基重复序列形成了一个延伸的α-螺旋，预计是周质的。ARP的建模揭示了C-末端孢子形成相关重复（SPOR）结构域，预测结合裸露的肽聚糖，重复区域可能并入高度带电的β-折叠。在重复序列之外，所有TP 0470和ARP氨基酸序列是相同的。总之，我们的数据，沿着功能的考虑，表明TP 0470和ARP蛋白可能参与T.苍白球细胞包膜重塑和稳态，其高度可塑性的重复区域发挥尚未确定的作用。
Sequencing of most Treponema pallidum genomes excludes repeat regions in tp0470 and the tp0433 gene, encoding the acidic repeat protein (arp). As a first step to understanding the evolution and function of these genes and the proteins they encode, we developed a protocol to nanopore sequence tp0470 and arp genes from 212 clinical samples collected from ten countries on six continents. Both tp0470 and arp repeat structures recapitulate the whole genome phylogeny, with subclade-specific patterns emerging. The number of tp0470 repeats is on average appears to be higher in Nichols-like clade strains than in SS14-like clade strains. Consistent with previous studies, we found that 14-repeat arp sequences predominate across both major clades, but the combination and order of repeat type varies among subclades, with many arp sequence variants limited to a single subclade. Although strains that were closely related by whole genome sequencing frequently had the same arp repeat length, this was not always the case. Structural modeling of TP0470 suggested that the eight residue repeats form an extended α-helix, predicted to be periplasmic. Modeling of the ARP revealed a C-terminal sporulation-related repeat (SPOR) domain, predicted to bind denuded peptidoglycan, with repeat regions possibly incorporated into a highly charged β-sheet. Outside of the repeats, all TP0470 and ARP amino acid sequences were identical. Together, our data, along with functional considerations, suggests that both TP0470 and ARP proteins may be involved in T. pallidum cell envelope remodeling and homeostasis, with their highly plastic repeat regions playing as-yet-undetermined roles.
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