Transcription of TP0126, Treponema pallidum Putative OmpW Homolog, Is Regulated by the Length of a Homopolymeric Guanosine Repeat
Transcription of TP0126, Treponema pallidum Putative OmpW Homolog, Is Regulated by the Length of a Homopolymeric Guanosine Repeat
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DOI：
10.1128/iai.00360-15
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发表时间：
2015-06-01
影响因子：
3.1
通讯作者：
Centurion-Lara, Arturo
中科院分区：
文献类型：
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作者：
Giacani, Lorenzo;Brandt, Stephanie L.;Centurion-Lara, Arturo
在细菌群体中引入表型多样性的有效机制是利用基因启动子内重复DNA元件长度的变化。这种现象称为相变，会导致基因表达快速激活或沉默，并促进细菌适应新的或不断变化的环境。相位变化经常发生在表面暴露的蛋白质和梅毒螺旋体亚种中。据报道，梅毒病原体梅毒会影响三个假定的外膜蛋白（OMP）编码基因的转录。当梅毒螺旋体亚种。苍白球 Nichols 菌株基因组最初被注释，TP0126 开放阅读框被预测包含聚 (G) 束，并且似乎不具有可能暗示其是 OMP 的可能性的预测信号序列。在这里，我们表明最初的注释是不正确的，该聚（G）反而位于TP0126启动子内，并且在实验性梅毒期间它在体内的长度发生变化。此外，我们还发现 TP0126 转录受到 Poly(G) 长度变化的影响，这与相位变化的调节一致。基于实验鉴定的转录起始位点对 TP0126 开放阅读框进行的计算机分析将该假设蛋白缩短了 69 个氨基酸，揭示了预测的可切割信号肽，并表明与 OmpW 孔蛋白家族的结构同源性。重组 TP0126 的圆二色性支持与 OmpW 的结构同源性。连同 TP0126 在梅毒螺旋体亚种和菌株中完全保守的证据一起，这些数据表明 TP0126 在梅毒螺旋体生物学和梅毒发病机制中发挥重要作用。
An effective mechanism for introduction of phenotypic diversity within a bacterial population exploits changes in the length of repetitive DNA elements located within gene promoters. This phenomenon, known as phase variation, causes rapid activation or silencing of gene expression and fosters bacterial adaptation to new or changing environments. Phase variation often occurs in surface-exposed proteins, and in Treponema pallidum subsp. pallidum, the syphilis agent, it was reported to affect transcription of three putative outer membrane protein (OMP)-encoding genes. When the Treponema pallidum subsp. pallidum Nichols strain genome was initially annotated, the TP0126 open reading frame was predicted to include a poly(G) tract and did not appear to have a predicted signal sequence that might suggest the possibility of its being an OMP. Here we show that the initial annotation was incorrect, that this poly(G) is instead located within the TP0126 promoter, and that it varies in length in vivo during experimental syphilis. Additionally, we show that TP0126 transcription is affected by changes in the poly(G) length consistent with regulation by phase variation. In silico analysis of the TP0126 open reading frame based on the experimentally identified transcriptional start site shortens this hypothetical protein by 69 amino acids, reveals a predicted cleavable signal peptide, and suggests structural homology with the OmpW family of porins. Circular dichroism of recombinant TP0126 supports structural homology to OmpW. Together with the evidence that TP0126 is fully conserved among Treponema pallidum subspecies and strains, these data suggest an important role for TP0126 in Treponema pallidum biology and syphilis pathogenesis.