The flagellar regulator fliT represses Salmonella pathogenicity island 1 through flhDC and fliZ.

The flagellar regulator fliT represses Salmonella pathogenicity island 1 through flhDC and fliZ.
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DOI:
10.1371/journal.pone.0034220
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发表时间:
2012
期刊:
影响因子:
3.7
通讯作者:
Altier C
Altier C
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Hung CC;Haines L;Altier C

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沙门氏菌致病性岛1(SPI 1)是肠道病原体沙门氏菌穿透肠上皮并随后引起疾病所必需的,其包含将效应蛋白易位到宿主细胞中的III型区段系统。使用随机转座子诱变,我们发现,一个Tn 10破坏鞭毛fliDST操纵子诱导SPI 1的表达时,该菌株生长的条件下,旨在抑制SPI 1,通过模仿大肠的环境,通过使用肠道脂肪酸丁酸。我们的遗传学研究表明,只有fliT在这个操纵子是需要这种效果,和外源性过度表达的fliT单独显着降低了SPI 1基因的表达,包括入侵调节hilA和sipBCDA操纵子,编码III型节系统效应蛋白,和沙门氏菌入侵培养的上皮细胞。已知fliT通过抑制鞭毛主调节因子flhDC来抑制鞭毛机器。我们发现,在没有flhDC或fliZ的情况下,fliT对侵袭基因的抑制作用被完全消除,后者先前显示诱导SPI 1,表明这种调节途径是fliT侵袭控制所必需的。虽然这种flhDC-fliZ通路是fliT负控制侵袭基因所必需的,但fliZ对于fliT对运动性的抑制作用不是必需的,从而使fliT在侵袭和运动性的调节级联中处于高位。
Salmonella pathogenicity island 1 (SPI1), comprising a type III section system that translocates effector proteins into host cells, is essential for the enteric pathogen Salmonella to penetrate the intestinal epithelium and subsequently to cause disease. Using random transposon mutagenesis, we found that a Tn10 disruption in the flagellar fliDST operon induced SPI1 expression when the strain was grown under conditions designed to repress SPI1, by mimicking the environment of the large intestine through the use of the intestinal fatty acid butyrate. Our genetic studies showed that only fliT within this operon was required for this effect, and that exogenous over-expression of fliT alone significantly reduced the expression of SPI1 genes, including the invasion regulator hilA and the sipBCDA operon, encoding type III section system effector proteins, and Salmonella invasion of cultured epithelial cells. fliT has been known to inhibit the flagellar machinery through repression of the flagellar master regulator flhDC. We found that the repressive effect of fliT on invasion genes was completely abolished in the absence of flhDC or fliZ, the latter previously shown to induce SPI1, indicating that this regulatory pathway is required for invasion control by fliT. Although this flhDC-fliZ pathway was necessary for fliT to negatively control invasion genes, fliZ was not essential for the repressive effect of fliT on motility, placing fliT high in the regulatory cascade for both invasion and motility.
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