Mapping the Regulatory Network for Salmonella enterica Serovar Typhimurium Invasion.
Mapping the Regulatory Network for Salmonella enterica Serovar Typhimurium Invasion.
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DOI：
10.1128/mbio.01024-16
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发表时间：
2016-09-06
期刊：
影响因子：
6.4
通讯作者：
Wade JT
中科院分区：
文献类型：
--
作者：
Smith C;Stringer AM;Mao C;Palumbo MJ;Wade JT
肠道沙门氏菌致病性岛1 （SPI-1）编码侵袭肠道上皮细胞所需的蛋白。入侵的时间由一个复杂的监管网络严格控制。转录因子（TF） HilD是这一过程的主要调节因子，并感知与入侵相关的环境信号。HilD激活SPI-1内外基因的转录，包括其他六种tf。因此，与宿主细胞侵袭相关的转录程序由至少7个tf控制。然而，已知的这些TFs的监管目标很少，监管网络的范围也不清楚。在这项研究中，我们使用互补的基因组方法来绘制所有7种tf的直接调控靶点。我们的数据揭示了一个高度复杂和相互关联的网络，其中包括许多以前未描述的监管目标。此外，由于包含了许多额外的tf和非编码rna，该网络远远超出了7个tf。通过比较7种TFs调控靶点的基因表达谱，我们发现了许多可能在入侵中起直接作用的未表征基因。我们还发现了SPI-1调控和其他调控途径之间的串扰，这反过来又确定了可能共享相关功能的基因簇。我们的数据可以通过一个直观的在线浏览器免费获得，并代表了细菌研究界的宝贵资源。侵袭上皮细胞是肠沙门氏菌感染的早期步骤，需要通过III型分泌系统（T3SS）向宿主细胞分泌特定蛋白。大多数入侵所需的t3ss相关蛋白编码在水平获得的基因组位点沙门氏菌致病性岛1 （SPI-1）中。多个调节因子响应环境信号，以确保适当的SPI-1基因表达时间。特别是，已知有7种转录调节因子参与SPI-1基因的协调表达。我们使用了互补的基因组尺度方法来绘制这七个调控因子的基因靶点。我们的数据揭示了一个高度复杂和相互关联的调控网络，其中包括许多以前未描述的靶基因。此外，我们的数据在功能上暗示了侵袭过程中许多未表征的基因，并揭示了SPI-1调控与其他调控途径之间的串扰。所有数据集都可以通过直观的在线浏览器免费获得。
Salmonella enterica pathogenicity island 1 (SPI-1) encodes proteins required for invasion of gut epithelial cells. The timing of invasion is tightly controlled by a complex regulatory network. The transcription factor (TF) HilD is the master regulator of this process and senses environmental signals associated with invasion. HilD activates transcription of genes within and outside SPI-1, including six other TFs. Thus, the transcriptional program associated with host cell invasion is controlled by at least 7 TFs. However, very few of the regulatory targets are known for these TFs, and the extent of the regulatory network is unclear. In this study, we used complementary genomic approaches to map the direct regulatory targets of all 7 TFs. Our data reveal a highly complex and interconnected network that includes many previously undescribed regulatory targets. Moreover, the network extends well beyond the 7 TFs, due to the inclusion of many additional TFs and noncoding RNAs. By comparing gene expression profiles of regulatory targets for the 7 TFs, we identified many uncharacterized genes that are likely to play direct roles in invasion. We also uncovered cross talk between SPI-1 regulation and other regulatory pathways, which, in turn, identified gene clusters that likely share related functions. Our data are freely available through an intuitive online browser and represent a valuable resource for the bacterial research community. Invasion of epithelial cells is an early step during infection by Salmonella enterica and requires secretion of specific proteins into host cells via a type III secretion system (T3SS). Most T3SS-associated proteins required for invasion are encoded in a horizontally acquired genomic locus known as Salmonella pathogenicity island 1 (SPI-1). Multiple regulators respond to environmental signals to ensure appropriate timing of SPI-1 gene expression. In particular, there are seven transcription regulators that are known to be involved in coordinating expression of SPI-1 genes. We have used complementary genome-scale approaches to map the gene targets of these seven regulators. Our data reveal a highly complex and interconnected regulatory network that includes many previously undescribed target genes. Moreover, our data functionally implicate many uncharacterized genes in the invasion process and reveal cross talk between SPI-1 regulation and other regulatory pathways. All datasets are freely available through an intuitive online browser.