The intestinal fatty acid propionate inhibits Salmonella invasion through the post-translational control of HilD.
The intestinal fatty acid propionate inhibits Salmonella invasion through the post-translational control of HilD.
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DOI：
10.1111/mmi.12149
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发表时间：
2013-03
影响因子：
3.6
通讯作者：
Altier C
中科院分区：
文献类型：
--
作者：
Hung CC;Garner CD;Slauch JM;Dwyer ZW;Lawhon SD;Frye JG;McClelland M;Ahmer BM;Altier C
沙门氏菌必须利用沙门氏菌致病岛1（SPI1）内编码的基因侵入肠上皮才能致病。我们在这里表明，丙酸，丰富的动物肠道中的脂肪酸，抑制SPI1在生理相关的浓度和pH值，减少SPI1转录调节因子的表达，从而减少效应蛋白的表达和分泌，导致减少细菌渗透培养的上皮细胞。抑制的关键是hilD，它占据了SPI1内调节级联的顶点，因为在调节子中只有这个基因的丢失阻止了丙酸盐对SPI1转录的抑制。然而，通过hilD的调节是通过既不控制转录也不控制翻译来实现的。相反，沙门氏菌在丙酸盐中的生长显著降低了HilD的稳定性。使用Lon蛋白酶突变体延长蛋白质半衰期表明，蛋白质稳定性本身并不决定丙酸盐的作用，并建议修改HilD与随后的降解作为行动的手段。此外，阻遏显着减少突变体不能产生丙酰辅酶A，而进一步代谢的丙酰辅酶A似乎是不需要的。这些结果表明了一种控制沙门氏菌毒力的机制，其中使用高能中间体丙酰辅酶A对HilD进行后修饰。
To cause disease, Salmonella must invade the intestinal epithelium employing genes encoded within Salmonella Pathogenicity Island 1 (SPI1). We show here that propionate, a fatty acid abundant in the intestine of animals, repressed SPI1 at physiologically relevant concentration and pH, reducing expression of SPI1 transcriptional regulators and consequently decreasing expression and secretion of effector proteins, leading to reduced bacterial penetration of cultured epithelial cells. Essential to repression was hilD, which occupies the apex of the regulatory cascade within SPI1, as loss of only this gene among those of the regulon prevented repression of SPI1 transcription by propionate. Regulation through hilD, however, was achieved through the control of neither transcription nor translation. Instead, growth of Salmonella in propionate significantly reduced the stability of HilD. Extending protein half-life using a Lon protease mutant demonstrated that protein stability itself did not dictate the effects of propionate and suggested modification of HilD with subsequent degradation as the means of action. Furthermore, repression was significantly lessened in a mutant unable to produce propionyl-CoA, while further metabolism of propionyl-CoA appeared not to be required. These results suggest a mechanism of control of Salmonella virulence in which HilD is post-translationally modified using the high energy intermediate propionyl-CoA.
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DOI：
10.1084/jem.139.5.1189
发表时间：
1974-05-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Carter PB;Collins FM
通讯作者：
Collins FM
影响因子：
3.6
作者：
Bajaj, V;Hwang, C;Lee, CA
通讯作者：
Lee, CA
影响因子：
3.5
作者：
Ellermeier, CD;Janakiraman, A;Slauch, JM
通讯作者：
Slauch, JM
影响因子：
3.2
作者：
Chubiz, Jessica E. Cott;Golubeva, Yekaterina A.;Slauch, James M.
通讯作者：
Slauch, James M.
影响因子：
3.1
作者：
Fortune, DR;Suyemoto, M;Altier, C
通讯作者：
Altier, C