Built shallow to maintain homeostasis and persistent infection: insight into the transcriptional regulatory network of the gastric human pathogen Helicobacter pylori.

Built shallow to maintain homeostasis and persistent infection: insight into the transcriptional regulatory network of the gastric human pathogen Helicobacter pylori.
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DOI:
10.1371/journal.ppat.1000938
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发表时间:
2010-06-10
期刊:
影响因子:
6.7
通讯作者:
Scarlato V
Scarlato V
中科院分区:
医学1区
文献类型:
--
作者:
Danielli A;Amore G;Scarlato V

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转录调控网络(TRN)将环境信号转化为基因组的协调输出表达。因此,它们是细菌适应其生活环境和宿主-病原体相互作用的中心。很少有人尝试描述人类病原体的TRN,因为即使在模式生物中,如大肠杆菌,分析也受到大量转录因子的阻碍。鉴于调节因子的缺乏,人类胃部病原体幽门螺杆菌代表了一个非常有吸引力的系统,以了解细菌TRN是如何连接在一起支持宿主感染的。在这里,我们回顾和分析了现有的分子和组学数据,包括与致病反应的转录控制相关的蛋白质-DNA和蛋白质-蛋白质相互作用。该分析覆盖了∼80%的注释幽门螺杆菌调节因子,并提供了据我们所知的第一个深入描述一个重要病原体的TRN。新出现的图片显示了一个浅的TRN,由四个主要模块(起源)组成,处理定植于胃壁龛所需的生理反应。特定的网络基序为TRN提供了不同的转录反应动力学,而没有长的调节级联。幽门螺杆菌的TRN似乎通过使用一小部分调节器的不同组合来传递不同的环境输入,而不是有过多的专门调节器。
Transcriptional regulatory networks (TRNs) transduce environmental signals into coordinated output expression of the genome. Accordingly, they are central for the adaptation of bacteria to their living environments and in host–pathogen interactions. Few attempts have been made to describe a TRN for a human pathogen, because even in model organisms, such as Escherichia coli, the analysis is hindered by the large number of transcription factors involved. In light of the paucity of regulators, the gastric human pathogen Helicobacter pylori represents a very appealing system for understanding how bacterial TRNs are wired up to support infection in the host. Herein, we review and analyze the available molecular and “-omic” data in a coherent ensemble, including protein–DNA and protein–protein interactions relevant for transcriptional control of pathogenic responses. The analysis covers ∼80% of the annotated H. pylori regulators, and provides to our knowledge the first in-depth description of a TRN for an important pathogen. The emerging picture indicates a shallow TRN, made of four main modules (origons) that process the physiological responses needed to colonize the gastric niche. Specific network motifs confer distinct transcriptional response dynamics to the TRN, while long regulatory cascades are absent. Rather than having a plethora of specialized regulators, the TRN of H. pylori appears to transduce separate environmental inputs by using different combinations of a small set of regulators.
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