A regulatory checkpoint during flagellar biogenesis in Campylobacter jejuni initiates signal transduction to activate transcription of flagellar genes.
A regulatory checkpoint during flagellar biogenesis in Campylobacter jejuni initiates signal transduction to activate transcription of flagellar genes.
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DOI：
10.1128/mbio.00432-13
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发表时间：
2013-09-03
期刊：
影响因子：
6.4
通讯作者：
Hendrixson DR
中科院分区：
文献类型：
--
作者：
Boll JM;Hendrixson DR
许多极鞭毛细菌需要类似的双组分调节系统（TCS）和σ54来激活鞭毛运动所必需的基因的转录。在此，我们发现，除了鞭毛III型分泌系统（T3 SS），空肠弯曲杆菌鞭毛MS环和转子需要激活FlgSR TCS。缺乏FliF MS环和FliG C环转子蛋白的突变体在FlgSR和σ54依赖性鞭毛基因表达方面与T3 SS突变体一样有缺陷。此外，FliF和FliG相互需要稳定性，这是由蛋白质的非典型延伸介导的。推测不与T3 SS蛋白FlhA相互作用的FliF突变体不支持鞭毛基因转录，表明FliF-T3 SS相互作用对于产生由细胞质FlgS组氨酸激酶感测的信号是必需的。此外，鞭毛T3 SS是FlgS与FliF和FliG免疫沉淀所必需的。我们提出了一个模型，鞭毛T3 SS促进FliF和FliG多聚化到MS环和转子。因此，这些鞭毛结构形成与FlgS相互作用并被FlgS感测的细胞质复合物。这些结构的合成似乎是鞭毛生物发生中的调节检查点，FlgS激酶监测该调节检查点以启动激活σ54的信号转导和下一阶段鞭毛形成所需的基因表达。考虑到其他极性鞭毛虫具有与空肠弯曲菌类似的鞭毛转录层次结构，这种调节检查点可能存在于广泛的细菌中，以影响类似的TCS和鞭毛基因转录。尽管细菌中存在许多双组分调节系统（TCS），但已知由TCS感知以激活信号转导的直接信号仅为少数。极性鞭毛虫，包括假单胞菌属、弧菌属、螺杆菌属和弯曲杆菌属，需要类似的TCS和σ54来进行鞭毛基因转录，但这些TCS的激活信号尚不清楚。我们探索了激活空肠弯曲杆菌FlgSR TCS以启动σ54依赖性鞭毛基因转录的信号。我们的发现表明，FlgS组氨酸激酶监测鞭毛III型分泌系统和周围的MS和C环的形成。这些结构的合成在鞭毛生物发生中产生了一个调节检查点，该检查点被FlgS感知，以确保下一组基因的正确转录，用于鞭毛形成的后续步骤。鉴于鞭毛相关的TCS和转录级联在极性鞭毛虫中的保守性，鞭毛生物发生中的这种调节检查点可能会影响广泛细菌中的鞭毛形成。
Many polarly flagellated bacteria require similar two-component regulatory systems (TCSs) and σ54 to activate transcription of genes essential for flagellar motility. Herein, we discovered that in addition to the flagellar type III secretion system (T3SS), the Campylobacter jejuni flagellar MS ring and rotor are required to activate the FlgSR TCS. Mutants lacking the FliF MS ring and FliG C ring rotor proteins were as defective as T3SS mutants in FlgSR- and σ54-dependent flagellar gene expression. Also, FliF and FliG required each other for stability, which is mediated by atypical extensions to the proteins. A FliF mutant that presumably does not interact with the T3SS protein FlhA did not support flagellar gene transcription, suggesting that FliF-T3SS interactions are essential to generate a signal sensed by the cytoplasmic FlgS histidine kinase. Furthermore, the flagellar T3SS was required for FlgS to immunoprecipitate with FliF and FliG. We propose a model whereby the flagellar T3SS facilitates FliF and FliG multimerization into the MS ring and rotor. As a result, these flagellar structures form a cytoplasmic complex that interacts with and is sensed by FlgS. The synthesis of these structures appears to be a regulatory checkpoint in flagellar biogenesis that the FlgS kinase monitors to initiate signal transduction that activates σ54 and expression of genes required for the next stage of flagellation. Given that other polar flagellates have flagellar transcriptional hierarchies that are organized similarly as in C. jejuni, this regulatory checkpoint may exist in a broad range of bacteria to influence similar TCSs and flagellar gene transcription. Despite the presence of numerous two-component regulatory systems (TCSs) in bacteria, direct signals sensed by TCSs to activate signal transduction are known for only a minority. Polar flagellates, including Pseudomonas, Vibrio, Helicobacter, and Campylobacter species, require a similar TCS and σ54 for flagellar gene transcription, but the activating signals for these TCSs are unknown. We explored signals that activate the Campylobacter jejuni FlgSR TCS to initiate σ54-dependent flagellar gene transcription. Our discoveries suggest that the FlgS histidine kinase monitors the formation of the flagellar type III secretion system and the surrounding MS and C rings. The synthesis of these structures creates a regulatory checkpoint in flagellar biogenesis that is sensed by FlgS to ensure proper transcription of the next set of genes for subsequent steps in flagellation. Given the conservation of flagellar-associated TCSs and transcriptional cascades in polar flagellates, this regulatory checkpoint in flagellar biogenesis likely impacts flagellation in a broad range of bacteria.