Control of a Salmonella virulence locus by an ATP-sensing leader messenger RNA.
Control of a Salmonella virulence locus by an ATP-sensing leader messenger RNA.
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DOI：
10.1038/nature11090
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发表时间：
2012-06-13
期刊：
影响因子：
64.8
通讯作者：
Groisman, Eduardo A.
中科院分区：
文献类型：
--
作者：
Lee, Eun-Jin;Groisman, Eduardo A.
肠道沙门氏菌是一种兼性的细胞内病原体，存在于巨噬细胞内的一个膜结合室内。沙门氏菌必须酸化才能在巨噬细胞内存活，这可能是因为酸性pH促进了沙门氏菌毒力蛋白的表达。我们推测，沙门氏菌可能感觉到它的周围环境已经变得酸性，不仅是因为蛋白质传感器的胞外结构域的质子化，而且是因为细胞内ATP水平的增加，因为增强细菌内膜上的质子梯度的条件刺激了ATP的合成。我们现在报道，细胞内ATP的增加促进了毒力基因MGTC编码区的转录，MGTC是沙门氏菌在巨噬细胞内时诱导最高的水平获得基因。这个转录本既是在介质酸化的情况下诱导的，也是在不依赖酸化的情况下增加ATP水平的生理条件下诱导的。ATP是通过异常长的MGTC前导mRNA转录的偶联/去偶联和位于该区域的一个短的开放阅读框架的翻译而被感知的。MGTC前导基因的突变消除了对三磷酸腺苷的反应，阻碍了巨噬细胞内MGTC的表达，并减弱了小鼠的沙门氏菌毒力。我们的结果定义了一个独特的三磷酸腺苷感应先导基因的例子。此外，他们指出，病原体可以通过它们对细胞代谢物的影响来解释细胞外线索。
The facultative intracellular pathogen Salmonella enterica resides within a membrane-bound compartment inside macrophages . This compartment must be acidified for Salmonella to survive within macrophages , possibly because acid pH promotes expression of Salmonella virulence proteins . We reasoned that Salmonella may sense its surroundings have turned acidic not only upon protonation of the extracytoplasmic domain of a protein sensor but also by an increase in cytosolic ATP levels because conditions that enhance the proton gradient across the bacterial inner membrane stimulate ATP synthesis . We now report that an increase in cytosolic ATP promotes transcription of the coding region for the virulence gene mgtC, which is the most highly-induced horizontally-acquired gene when Salmonella is inside macrophages . This transcript was induced both upon media acidification as well as by physiological conditions that increase ATP levels independently of acidification. ATP is sensed via the coupling/uncoupling of transcription of the unusually long mgtC leader mRNA and translation of a short open reading frame located in this region. A mutation in the mgtC leader mRNA that eliminated the response to ATP hindered mgtC expression inside macrophages and attenuated Salmonella virulence in mice. Our results define a singular example of an ATP-sensing leader mRNA. Moreover, they indicate that pathogens can interpret extracellular cues by the impact they have on cellular metabolites.
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影响因子：
3.6
作者：
Lee EJ;Groisman EA
通讯作者：
Groisman EA
影响因子：
5.6
作者：
Chamnongpol, S;Groisman, EA
通讯作者：
Groisman, EA
影响因子：
2.9
作者：
JENSEN, KF;HOULBERG, U;NYGAARD, P
通讯作者：
NYGAARD, P
DOI：
10.1073/pnas.94.3.934
发表时间：
1997-02-04
影响因子：
11.1
作者：
Heithoff, DM;Conner, CP;Mahan, MJ
通讯作者：
Mahan, MJ
影响因子：
56.9
作者：
Dennis, PB;Jaeschke, A;Thomas, G
通讯作者：
Thomas, G