Treponema pallidum subsp. pallidum TP0136 protein is heterogeneous among isolates and binds cellular and plasma fibronectin via its NH2-terminal end.
Treponema pallidum subsp. pallidum TP0136 protein is heterogeneous among isolates and binds cellular and plasma fibronectin via its NH2-terminal end.
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DOI：
10.1371/journal.pntd.0003662
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发表时间：
2015-03
影响因子：
3.8
通讯作者：
Giacani L
中科院分区：
文献类型：
--
作者：
Ke W;Molini BJ;Lukehart SA;Giacani L
粘附介导的定殖在微生物感染的发病机制中起重要作用，特别是那些由引起全身性疾病的细胞外病原体引起的微生物感染，例如梅毒螺旋体（Treponema pallidum subsp.苍白球（T. pallidum），梅毒的媒介。在T.已知苍白球粘附素TP 0136结合宿主细胞外基质的重要成分纤连蛋白（Fn）。为了加深我们对TP 0136-Fn相互作用动力学的理解，我们使用TP 0136蛋白的两个天然存在的序列变体来研究蛋白质的哪个区域负责Fn结合，以及TP 0136是否会如先前报道的那样除了血浆Fn和超级Fn之外还粘附于人细胞Fn。用代表两种全长TP 0136变体及其离散区域的重组蛋白进行Fn结合测定。作为补充方法，我们测试了T.通过重组全长TP 0136蛋白和片段以及通过抗TP 0136免疫血清测定苍白球与Fn的结合。我们的研究结果表明，TP 0136更有效地坚持细胞Fn比血浆Fn，TP 0136 NH 2-末端保守区的蛋白质是主要负责结合血浆Fn，但细胞Fn的结合位点也存在于蛋白质的中央和COOH-末端区域。此外，信息定量研究表明，tp 0136在实验感染期间高度转录，并且其信息水平与宿主对病原体的免疫压力平行增加，这表明该蛋白在T.苍白球持续性在梅毒发病率很高的时候，我们的数据将有助于寻找合适的目标，以开发急需的疫苗来对抗这种重要的疾病。梅毒螺旋体的研究。苍白球（T. pallidum）蛋白质，其介导与宿主组织成分的粘附，对于理解梅毒病原体如何建立感染以及在从进入部位传播后能够侵入几乎每个器官系统是关键的。本研究以T. pallidum TP 0136是一种已知的血浆纤连蛋白（Fn）和超Fn结合蛋白，在T.苍白球分离株这项研究表明，TP 0136还介导附着到人细胞Fn，TP 0136保守的NH 2-末端主要负责结合血浆Fn，但细胞Fn结合位点似乎分散在整个分子中。信息定量实验表明，tp 0136转录是高的实验梅毒和细菌免疫清除的时间增加，这表明该抗原在抵消宿主防御感染期间的作用，在其他病原体中的其他Fn结合蛋白的报告。我们的数据加深了目前对T. pallidum TP 0136的研究，并进一步支持该毒力因子在梅毒发病机制中的作用。
Adherence-mediated colonization plays an important role in pathogenesis of microbial infections, particularly those caused by extracellular pathogens responsible for systemic diseases, such as Treponema pallidum subsp. pallidum (T. pallidum), the agent of syphilis. Among T. pallidum adhesins, TP0136 is known to bind fibronectin (Fn), an important constituent of the host extracellular matrix. To deepen our understanding of the TP0136-Fn interaction dynamics, we used two naturally-occurring sequence variants of the TP0136 protein to investigate which region of the protein is responsible for Fn binding, and whether TP0136 would adhere to human cellular Fn in addition to plasma Fn and super Fn as previously reported. Fn binding assays were performed with recombinant proteins representing the two full-length TP0136 variants and their discrete regions. As a complementary approach, we tested inhibition of T. pallidum binding to Fn by recombinant full-length TP0136 proteins and fragments, as well as by anti-TP0136 immune sera. Our results show that TP0136 adheres more efficiently to cellular Fn than to plasma Fn, that the TP0136 NH2-terminal conserved region of the protein is primarily responsible for binding to plasma Fn but that binding sites for cellular Fn are also present in the protein’s central and COOH-terminal regions. Additionally, message quantification studies show that tp0136 is highly transcribed during experimental infection, and that its message level increases in parallel to the host immune pressure on the pathogen, which suggests a possible role for this protein in T. pallidum persistence. In a time where syphilis incidence is high, our data will help in the quest to identify suitable targets for development of a much needed vaccine against this important disease. The study of Treponema pallidum subsp. pallidum (T. pallidum) proteins that mediate adhesion to host tissue components is pivotal to understand how the syphilis agent establishes infection and is able to invade virtually every organ system following dissemination from the site of entry. This study focuses on T. pallidum TP0136, a known plasma fibronectin (Fn) and super Fn binding protein that is heterogeneous in sequence among T. pallidum isolates. This study shows that TP0136 also mediates attachment to human cellular Fn, that TP0136 conserved NH2-terminus is primarily responsible for binding to plasma Fn, but that cellular Fn binding sites appears to be scattered throughout the molecule. Message quantification experiments reveal that tp0136 transcription is high during experimental syphilis and increases at the time of bacterial immune clearance, suggesting a role for this antigen in counteracting the host defenses during infection, as reported for other Fn binding proteins in other pathogens. Our data deepen the current knowledge of the function of T. pallidum TP0136 and further support a role for this virulence factor in syphilis pathogenesis.
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影响因子：
3.2
作者：
Giacani, Lorenzo;Denisenko, Oleg;Centurion-Lara, Arturo
通讯作者：
Centurion-Lara, Arturo
DOI：
10.1111/j.1467-842x.2006.tb00781.x
发表时间：
2006-12-01
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影响因子：
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