TprK sequence diversity accumulates during infection of rabbits with Treponema pallidum subsp pallidum Nichols straint
TprK sequence diversity accumulates during infection of rabbits with Treponema pallidum subsp pallidum Nichols straint
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DOI：
10.1128/iai.74.3.1896-1906.2006
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发表时间：
2006-03-01
影响因子：
3.1
通讯作者：
Lukehart, SA
中科院分区：
文献类型：
--
作者：
LaFond, RE;Centurion-Lara, A;Lukehart, SA
梅毒螺旋体tprK基因发生抗原性变异。除Nichols型菌株外，在迄今检测的所有梅毒螺旋体分离株中，都已鉴定出异质性tprK序列。这种异质性被定位在7个可变区，tprK序列多样性在幼兔体内随着连续传代而积累。梅毒螺旋体Nichols基因组描述了一个单一的tprK序列，经过几十年的独立传代，来自不同实验室的Nichols菌株之间只有很小的tprK序列差异。我们假设梅毒螺旋体只能进行有限的tprk多样化。为了解决这一假设，我们在感染的高峰期(快速传代)或在适应性免疫反应清除了体内大多数生物体之后(缓慢传代)，在幼兔身上传代了梅毒螺旋体尼科尔斯株。经过22次快速传代(间隔9-10天)，没有观察到tprK V区序列的变化。相反，在两次缓慢传代(间隔30至35天)后，三个V区的序列与原始接种完全不同。在第五次慢传代时，在所有七个V区都观察到了新的序列。与快速传代的Nichols株不同，快速传代的芝加哥C株是从高度多样化的亲本芝加哥株中分离出来的克隆株，具有显著的tprK多样性。这些发现表明，在Nichols中可以发生tprK变异，但变异的速度较低，并且可能需要免疫压力来积累具有不同tprK序列的细菌。兔对生长的适应可以解释在Nichols品系中看到的V区序列的有限谱系。
The tprK gene in Treponema pallidum undergoes antigenic variation. In all T. pallidum isolates examined to date, except the Nichols type strain, heterogeneous tprK sequences have been identified. This heterogeneity is localized to seven variable (V) regions, and tprK sequence diversity accumulates with serial passage in naive rabbits. The T. pallidum Nichols genome described a single tprK sequence, and after decades of independent passage, only minor tprK sequence diversity is seen among the Nichols strains from different laboratories. We hypothesized that T. pallidum Nichols is capable of only limited tprK diversification. To address this hypothesis, we passaged the T. pallidum Nichols strain in naive rabbits at the peak of infection (rapid passage) or after the adaptive immune response had cleared most organisms in vivo (slow passage). After 22 rapid passages (9- to 10-day intervals), no tprK V region sequence changes were observed. In contrast, after two slow passages (30- to 35-day intervals), three V regions had sequences that were completely different from that of the original inoculum. New sequences were observed in all seven V regions by the fifth slow passage. In contrast to the rapid-passaged Nichols strain, rapid-passaged Chicago C, a clonal strain isolated from the highly diverse parent Chicago strain, developed significant tprK diversification. These findings suggest that tprK variation can occur, but at a lower rate, in Nichols and that immune pressure may be required for accumulation of bacteria with diverse tprK sequences. Adaptation to growth in rabbits may explain the limited repertoire of V region sequences seen in the Nichols strain.