The Pseudomonas aeruginosa Chp chemosensory system regulates intracellular cAMP levels by modulating adenylate cyclase activity.

The Pseudomonas aeruginosa Chp chemosensory system regulates intracellular cAMP levels by modulating adenylate cyclase activity.
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DOI:
10.1111/j.1365-2958.2010.07135.x
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发表时间:
2010-05
影响因子:
3.6
通讯作者:
Wolfgang MC
Wolfgang MC
中科院分区:
生物学2区
文献类型:
--
作者:
Fulcher NB;Holliday PM;Klem E;Cann MJ;Wolfgang MC

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条件致病菌铜绿假单胞菌的多个毒力系统受第二信使信号分子腺苷3′,5′-环单磷酸腺苷(cAMP)的调控。腺苷酸环化酶CyaB产生cAMP是毒力基因调控的关键控制点。为了鉴定CyaB的调节因子,我们筛选了一个转座子插入文库,用于细胞内cAMP减少的突变体。大多数导致cAMP减少的插入定位于Chp基因簇,该基因簇编码一个假定的趋化样化学感觉系统。进一步的遗传分析表明,Chp系统对细胞内cAMP有积极和消极的影响,并通过调节CyaB活性来调节cAMP水平。Chp系统先前与IV型菌毛(TFP)的产生和功能有关。鉴于cAMP和cAMP依赖的转录调控因子Vfr控制TFP生物发生基因的表达,我们探索了cAMP、Chp系统和TFP调控之间的关系。我们发现Chp系统通过调节cAMP来控制TFP的产生,而对TFP依赖的抽搐运动的控制与cAMP无关。总的来说,我们的数据定义了趋化样系统在控制cAMP产生方面的新功能,并在Chp系统、TFP和其他cAMP依赖性毒力系统之间建立了监管联系。
Multiple virulence systems in the opportunistic pathogen Pseudomonas aeruginosa are regulated by the second messenger signaling molecule adenosine 3’, 5’-cyclic monophosphate (cAMP). Production of cAMP by the putative adenylate cyclase enzyme CyaB represents a critical control point for virulence gene regulation. To identify regulators of CyaB, we screened a transposon insertion library for mutants with reduced intracellular cAMP. The majority of insertions resulting in reduced cAMP mapped to the Chp gene cluster encoding a putative chemotaxis-like chemosensory system. Further genetic analysis of the Chp system revealed that it has both positive and negative effects on intracellular cAMP and that it regulates cAMP levels by modulating CyaB activity. The Chp system was previously implicated in the production and function of type IV pili (TFP). Given that cAMP and the cAMP-dependent transcriptional regulator Vfr control TFP biogenesis gene expression, we explored the relationship between cAMP, the Chp system and TFP regulation. We discovered that the Chp system controls TFP production through modulation of cAMP while control of TFP-dependent twitching motility is cAMP-independent. Overall, our data define a novel function for a chemotaxis-like system in controlling cAMP production and establish a regulatory link between the Chp system, TFP and other cAMP-dependent virulence systems.
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