LaFond Rebecca E, Centurion-Lara Arturo, Godornes Charmie, Van Voorhis Wesley C, Lukehart Sheila A
Department of Pathobiology, Box 359779, Harborview Medical Center, 325 Ninth Ave., Seattle, WA 98104, USA.
Infect Immun. 2006 Mar;74(3):1896-906. doi: 10.1128/IAI.74.3.1896-1906.2006.
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 naïve 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 naïve 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.
梅毒螺旋体中的tprK基因会发生抗原变异。在迄今为止检测的所有梅毒螺旋体分离株中，除了Nichols标准菌株外，均已鉴定出异质性的tprK序列。这种异质性定位于七个可变（V）区域，并且tprK序列多样性会随着在未感染过的兔子中连续传代而积累。梅毒螺旋体Nichols基因组描述了单一的tprK序列，经过数十年的独立传代后，在来自不同实验室的Nichols菌株中仅观察到微小的tprK序列多样性。我们推测梅毒螺旋体Nichols仅能进行有限的tprK多样化。为了验证这一推测，我们在感染高峰期（快速传代）或在适应性免疫反应清除了体内大多数生物体后（缓慢传代），将梅毒螺旋体Nichols菌株接种到未感染过的兔子体内。经过22次快速传代（间隔9至10天）后，未观察到tprK V区域序列变化。相比之下，经过两次缓慢传代（间隔30至35天）后，三个V区域的序列与原始接种物完全不同。到第五次缓慢传代时，在所有七个V区域均观察到了新序列。与快速传代的Nichols菌株不同，从高度多样化的亲本芝加哥菌株中分离出的克隆菌株芝加哥C快速传代后，出现了显著的tprK多样化。这些发现表明，tprK变异在Nichols菌株中可能会发生，但频率较低，并且积累具有不同tprK序列的细菌可能需要免疫压力。对在兔子体内生长的适应性可能解释了在Nichols菌株中观察到的有限的V区域序列库。
