Systematic analysis of cyclic di-GMP signalling enzymes and their role in biofilm formation and virulence in Yersinia pestis.
Systematic analysis of cyclic di-GMP signalling enzymes and their role in biofilm formation and virulence in Yersinia pestis.
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DOI：
10.1111/j.1365-2958.2010.07470.x
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发表时间：
2011-01
影响因子：
3.6
通讯作者：
Perry RD
中科院分区：
文献类型：
--
作者：
Bobrov AG;Kirillina O;Ryjenkov DA;Waters CM;Price PA;Fetherston JD;Mack D;Goldman WE;Gomelsky M;Perry RD
环二-GMP（c-di-GMP）是一种信号分子，其控制着生物膜状态和非生物膜状态之间的转变。以前我们发现，双鸟苷酸环化酶HmsT和假定的c-di-GMP磷酸二酯酶HmsP通过控制HmsHFRS依赖性聚-β-1，6-N-乙酰葡糖胺合成来反向调节生物膜形成。在这里，我们系统地研究了鼠疫耶尔森氏菌中编码推定的c-di-GMP代谢酶的基因的功能。我们确定，除了hmsT和hmsP，只有基因y3730编码的功能酶能够合成c-di-GMP。剩下的7个基因是假基因或编码不起催化作用或不表达的蛋白质。此外，我们表明，HmsP具有C-二GMP特异性磷酸二酯酶活性。我们报告说，突变体不能合成的c-di-GMP是鼠疫小鼠模型的毒力不受影响。相反，不能降解c-di-GMP的hmsP突变体由于聚-β-1，6-N-乙酰葡糖胺的过量产生而通过皮下途径感染而在毒力上有缺陷。这表明，c-di-GMP信号不仅是有害的，而且对Y。鼠疫毒力我们的研究结果表明，在Y.与来自祖先假结核耶尔森氏菌的鼠疫相比，其c-di-GMP信号传导网络的复杂性显著降低，这可能是由这些人类病原体的不同疾病周期引起的。
Cyclic di-GMP (c-di-GMP) is a signaling molecule that governs the transition between planktonic and biofilm states. Previously we showed that the diguanylate cyclase HmsT and the putative c-di-GMP phosphodiesterase HmsP inversely regulate biofilm formation through control of HmsHFRS-dependent poly-β-1,6-N-acetylglucosamine synthesis. Here, we systematically examine the functionality of the genes encoding putative c-di-GMP metabolic enzymes in Yersinia pestis. We determine that, in addition to hmsT and hmsP, only the gene y3730 encodes a functional enzyme capable of synthesizing c-di-GMP. The seven remaining genes are pseudogenes or encode proteins that do not function catalytically or are not expressed. Furthermore, we show that HmsP has c-di-GMP-specific phosphodiesterase activity. We report that a mutant incapable of c-di-GMP synthesis is unaffected in virulence in plague mouse models. Conversely, an hmsP mutant, unable to degrade c-di-GMP, is defective in virulence by a subcutaneous route of infection due to poly-β-1,6-N-acetylglucosamine overproduction. This suggests that c-di-GMP signaling is not only dispensable but deleterious for Y. pestis virulence. Our results show that a key event in the evolution of Y. pestis from the ancestral Yersinia pseudotuberculosis was a significant reduction in the complexity of its c-di-GMP signaling network likely resulting from the different disease cycles of these human pathogens.
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影响因子：
4.2
作者：
Galperin MY
通讯作者：
Galperin MY
影响因子：
36.8
作者：
BRUBAKER, RR
通讯作者：
BRUBAKER, RR
影响因子：
5.1
作者：
Bobrov, Alexander G.;Kirillina, Olga;Perry, Robert D.
通讯作者：
Perry, Robert D.
影响因子：
3.1
作者：
Fetherston, Jacqueline D.;Kirillina, Olga;Perry, Robert D.
通讯作者：
Perry, Robert D.
DOI：
10.1073/pnas.120163297
发表时间：
2000-06-06
影响因子：
11.1
作者：
Datsenko, KA;Wanner, BL
通讯作者：
Wanner, BL