Identification of the Treponema pallidum subsp pallidum TP0092 (RpoE) Regulon and Its Implications for Pathogen Persistence in the Host and Syphilis Pathogenesis
Identification of the Treponema pallidum subsp pallidum TP0092 (RpoE) Regulon and Its Implications for Pathogen Persistence in the Host and Syphilis Pathogenesis
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DOI：
10.1128/jb.01973-12
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发表时间：
2013-02-01
影响因子：
3.2
通讯作者：
Centurion-Lara, Arturo
中科院分区：
文献类型：
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作者：
Giacani, Lorenzo;Denisenko, Oleg;Centurion-Lara, Arturo
细菌通常通过诱导细胞质外功能（ECF）σ（sigma）因子来响应有害的环境刺激，所述因子继而指导RNA聚合酶转录特定组的响应基因（或调节子）以最小化细胞损伤并有利于适应改变的细胞外环境。梅毒螺旋体（Treponema pallidum subsp.）在梅毒病原体（pallidum）中，TP 0092基因被预测编码病原体的唯一注释的ECF σ因子，其与大肠杆菌中已知的RpoE同源，以控制响应于外部应激和细胞生长而维持包膜稳态的关键转导途径。在这里，我们已经表明，TP 0092是高度转录在实验梅毒。此外，随着感染向病原体的免疫清除进展，TP 0092转录水平显着增加，这表明TP 0092在帮助T.苍白球对宿主环境中的有害刺激有反应。为了研究这一假设，我们使用染色质免疫沉淀法，然后进行高通量测序，在感染期间的两个不同时间点确定了TP 0092调节子。总共22个染色体区域，全部含有推定的TP 0092结合位点，并且对应于尽可能多的T. pallidum基因。其中值得注意的是编码铁氧还蛋白和硫氧还蛋白的基因，它们参与活性氧（ROS）的解毒。因为T.虽然梅毒螺旋体不具有其它用于ROS解毒的酶，如超氧化物歧化酶、过氧化氢酶或谷胱甘肽过氧化物酶，但我们的结果表明TP 0092调节子在保护梅毒螺旋体免受炎症反应期间在感染部位产生的ROS引起的损伤方面是重要的。
Bacteria often respond to harmful environmental stimuli with the induction of extracytoplasmic function (ECF) sigma (sigma) factors that in turn direct RNA polymerase to transcribe specific groups of response genes (or regulons) to minimize cellular damage and favor adaptation to the changed extracellular milieu. In Treponema pallidum subsp. pallidum, the agent of syphilis, the TP0092 gene is predicted to code for the pathogen's only annotated ECF sigma factor, homologous to RpoE, known in Escherichia coli to control a key transduction pathway for maintenance of envelope homeostasis in response to external stress and cell growth. Here we have shown that TP0092 is highly transcribed during experimental syphilis. Furthermore, TP0092 transcription levels significantly increase as infection progresses toward immune clearance of the pathogen, suggesting a role for TP0092 in helping T. pallidum respond to harmful stimuli in the host environment. To investigate this hypothesis, we determined the TP0092 regulon at two different time points during infection using chromatin immunoprecipitation followed by high-throughput sequencing. A total of 22 chromosomal regions, all containing putative TP0092-binding sites and corresponding to as many T. pallidum genes, were identified. Noteworthy among them are the genes encoding desulfoferrodoxin and thioredoxin, involved in detoxification of reactive oxygen species (ROS). Because T. pallidum does not possess other enzymes for ROS detoxification, such as superoxide dismutase, catalase, or glutathione peroxidase, our results suggest that the TP0092 regulon is important in protecting the syphilis spirochete from damage caused by ROS produced at the site of infection during the inflammatory response.