Wadsworth Center, New York State Department of Health, Albany, New York, USA.
J Bacteriol. 2014 Mar;196(5):1094-101. doi: 10.1128/JB.01449-13. Epub 2013 Dec 27.
Salmonella enterica serovar Typhimurium (S. Typhimurium) pathogenicity island 1 (SPI-1) encodes a type III secretion system required for invasion of host gut epithelial cells. Expression of SPI-1 virulence genes is controlled by a complex hierarchy of transcription factors encoded within and outside SPI-1. The master regulator of SPI-1, HilA, is itself regulated by three homologous transcription factors, HilD, HilC, and RtsA. HilD activates transcription of hilA and other target genes in response to environmental conditions associated with the intestinal microenvironment of the host. We have mapped the binding of HilD across the S. Typhimurium genome using chromatin immunoprecipitation-sequencing (ChIP-seq). Thus, we have identified 17 regions bound by HilD, including 11 novel targets. The majority of HilD targets are located outside SPI-1. We demonstrate transcription activation of 8 genes by HilD; four of these genes have not been previously described as being regulated by HilD, including lpxR, which encodes a lipid A deacylase important for immune evasion. We also show that HilD-activated genes are frequently activated by HilC and RtsA, indicating extensive overlap of the HilD, HilC, and RtsA regulons.
鼠伤寒沙门氏菌血清型 Typhimurium（S. Typhimurium）致病性岛 1（SPI-1）编码一种需要入侵宿主肠道上皮细胞的 III 型分泌系统。SPI-1 毒力基因的表达受 SPI-1 内外编码的复杂转录因子层次结构控制。SPI-1 的主要调节因子 HilA 自身受三个同源转录因子 HilD、HilC 和 RtsA 的调节。HilD 响应与宿主肠道微环境相关的环境条件，激活 hilA 和其他靶基因的转录。我们使用染色质免疫沉淀测序（ChIP-seq）在鼠伤寒沙门氏菌全基因组上绘制了 HilD 的结合图谱。因此，我们确定了 HilD 结合的 17 个区域，包括 11 个新的靶标。大多数 HilD 靶标位于 SPI-1 之外。我们证明 HilD 可转录激活 8 个基因；其中 4 个基因以前没有被描述为受 HilD 调节，包括编码对免疫逃避很重要的脂 A 脱酰酶的 lpxR。我们还表明，HilD 激活的基因经常被 HilC 和 RtsA 激活，表明 HilD、HilC 和 RtsA 调节子之间存在广泛的重叠。
