Complete genome sequence of Treponema pallidum ssp. pallidum strain SS14 determined with oligonucleotide arrays.

Complete genome sequence of Treponema pallidum ssp. pallidum strain SS14 determined with oligonucleotide arrays.
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DOI:
10.1186/1471-2180-8-76
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发表时间:
2008-05-15
期刊:
影响因子:
4.2
通讯作者:
Weinstock, George M.
Weinstock, George M.
中科院分区:
生物学3区
文献类型:
--
作者:
Matejkova, Petra;Strouhal, Michal;Smajs, David;Norris, Steven J.;Palzkill, Timothy;Petrosino, Joseph F.;Sodergren, Erica;Norton, Jason E.;Singh, Jaz;Richmond, Todd A.;Molla, Michael N.;Albert, Thomas J.;Weinstock, George M.

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梅毒螺旋体梅毒螺旋体亚种。苍白球仍然是神秘的病原体,因为没有确定毒力因子,并且对该疾病的发病机制知之甚少。最近观察到每年新发梅毒病例的比率在增加。通过仅需要与三个阵列杂交的寡核苷酸阵列策略(比较基因组测序,CGS)对SS14菌株的基因组进行高准确度测序。用靶向双脱氧终止子(DDT)测序填补所得序列中的缺口,并通过全基因组指纹(WGF)确认序列。与Nichols株相比,发现了327个单核苷酸替换(224个转换,103个颠换),14个缺失和18个插入。在蛋白质组水平上,氨基酸改变替换多态性的频率最高的是新基因,而最低的是管家基因,正如其进化保守性所预期的那样。在T.苍白球染色体观察到的遗传变化对梅毒螺旋体引起梅毒感染的能力没有影响,因为SS14和Nichols在兔中都是有毒的。然而,这是第一次评估两种梅毒病原体之间的变异程度,并为这种迷人的生物体的系统发育研究铺平了道路。
Syphilis spirochete Treponema pallidum ssp. pallidum remains the enigmatic pathogen, since no virulence factors have been identified and the pathogenesis of the disease is poorly understood. Increasing rates of new syphilis cases per year have been observed recently. The genome of the SS14 strain was sequenced to high accuracy by an oligonucleotide array strategy requiring hybridization to only three arrays (Comparative Genome Sequencing, CGS). Gaps in the resulting sequence were filled with targeted dideoxy-terminators (DDT) sequencing and the sequence was confirmed by whole genome fingerprinting (WGF). When compared to the Nichols strain, 327 single nucleotide substitutions (224 transitions, 103 transversions), 14 deletions, and 18 insertions were found. On the proteome level, the highest frequency of amino acid-altering substitution polymorphisms was in novel genes, while the lowest was in housekeeping genes, as expected by their evolutionary conservation. Evidence was also found for hypervariable regions and multiple regions showing intrastrain heterogeneity in the T. pallidum chromosome. The observed genetic changes do not have influence on the ability of Treponema pallidum to cause syphilitic infection, since both SS14 and Nichols are virulent in rabbit. However, this is the first assessment of the degree of variation between the two syphilis pathogens and paves the way for phylogenetic studies of this fascinating organism.
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