Department of Medicine, University of Washington, Seattle, WA, USA.
PLoS Negl Trop Dis. 2012;6(6):e1698. doi: 10.1371/journal.pntd.0001698. Epub 2012 Jun 12.
In the rabbit model of syphilis, infection phenotypes associated with the Nichols and Chicago strains of Treponema pallidum (T. pallidum), though similar, are not identical. Between these strains, significant differences are found in expression of, and antibody responses to some candidate virulence factors, suggesting the existence of functional genetic differences between isolates. The Chicago strain genome was therefore sequenced and compared to the Nichols genome, available since 1998. Initial comparative analysis suggested the presence of 44 single nucleotide polymorphisms (SNPs), 103 small (≤3 nucleotides) indels, and 1 large (1204 bp) insertion in the Chicago genome with respect to the Nichols genome. To confirm the above findings, Sanger sequencing was performed on most loci carrying differences using DNA from Chicago and the Nichols strain used in the original T. pallidum genome project. A majority of the previously identified differences were found to be due to errors in the published Nichols genome, while the accuracy of the Chicago genome was confirmed. However, 20 SNPs were confirmed between the two genomes, and 16 (80.0%) were found in coding regions, with all being of non-synonymous nature, strongly indicating action of positive selection. Sequencing of 16 genomic loci harboring SNPs in 12 additional T. pallidum strains, (SS14, Bal 3, Bal 7, Bal 9, Sea 81-3, Sea 81-8, Sea 86-1, Sea 87-1, Mexico A, UW231B, UW236B, and UW249C), was used to identify "Chicago-" or "Nichols -specific" differences. All but one of the 16 SNPs were "Nichols-specific", with Chicago having identical sequences at these positions to almost all of the additional strains examined. These mutations could reflect differential adaptation of the Nichols strain to the rabbit host or pathoadaptive mutations acquired during human infection. Our findings indicate that SNPs among T. pallidum strains emerge under positive selection and, therefore, are likely to be functional in nature.
在梅毒的兔模型中，与苍白密螺旋体的 Nichols 和芝加哥株相关的感染表型虽然相似，但并不完全相同。在这些菌株之间，一些候选毒力因子的表达和抗体反应存在显著差异，这表明分离株之间存在功能遗传差异。因此，对芝加哥株的基因组进行了测序，并与 1998 年以来可用的 Nichols 基因组进行了比较。初步比较分析表明，芝加哥基因组相对于 Nichols 基因组存在 44 个单核苷酸多态性（SNP）、103 个小（≤3 个核苷酸）插入缺失和 1 个大（1204bp）插入。为了确认上述发现，使用来自芝加哥株和原始苍白密螺旋体基因组项目中使用的 Nichols 株的 DNA，对携带差异的大多数基因座进行了 Sanger 测序。大多数先前确定的差异是由于 Nichols 基因组的发布错误，而芝加哥基因组的准确性得到了确认。然而，在两个基因组之间确认了 20 个 SNP，其中 16 个（80.0%）位于编码区，均为非同义性质，这强烈表明正选择作用。对 12 株额外的苍白密螺旋体菌株（SS14、Bal 3、Bal 7、Bal 9、Sea 81-3、Sea 81-8、Sea 86-1、Sea 87-1、Mexico A、UW231B、UW236B 和 UW249C）中携带 SNP 的 16 个基因组基因座进行测序，以鉴定“芝加哥株特异性”或“Nichols 株特异性”差异。在这 16 个 SNP 中，除了 1 个之外，其余均为“Nichols 株特异性”，芝加哥株在这些位置的序列与几乎所有被检测的额外菌株相同。这些突变可能反映了 Nichols 株对兔宿主的不同适应或在人类感染期间获得的病理适应突变。我们的研究结果表明，苍白密螺旋体菌株之间的 SNP 是在正选择下产生的，因此，其性质很可能是功能性的。
