Departamento de Microbiología Molecular, Instituto de Biotecnología, Universidad Nacional Autónoma de México, Cuernavaca, Morelos, 62210, Mexico.
Sci Rep. 2019 Sep 4;9(1):12725. doi: 10.1038/s41598-019-49192-z.
HilD is an AraC-like transcriptional regulator encoded in the Salmonella pathogenicity island 1 (SPI-1), which actives transcription of many genes within and outside SPI-1 that are mainly required for invasion of Salmonella into host cells. HilD controls expression of target genes directly or by acting through distinct regulators; three different regulatory cascades headed by HilD have been described to date. Here, by analyzing the effect of HilD on the yobH gene in Salmonella enterica serovar Typhimurium (S. Typhimurium), we further define an additional regulatory cascade mediated by HilD, which was revealed by previous genome-wide analyses. In this regulatory cascade, HilD acts through SprB, a LuxR-like regulator encoded in SPI-1, to induce expression of virulence genes. Our data show that HilD induces expression of sprB by directly counteracting H-NS-mediated repression on the promoter region upstream of this gene. Then, SprB directly activates expression of several genes including yobH, slrP and ugtL. Interestingly, we found that YobH, a protein of only 79 amino acids, is required for invasion of S. Typhimurium into HeLa cells and mouse macrophages. Thus, our results reveal a novel S. Typhimurium invasion factor and provide more evidence supporting the HilD-SprB regulatory cascade.
HilD 是沙门氏菌致病岛 1（SPI-1）中编码的 AraC 样转录调节因子，它激活 SPI-1 内和外的许多基因的转录，这些基因主要用于沙门氏菌侵入宿主细胞。HilD 直接或通过作用于不同的调节因子来控制靶基因的表达；迄今为止，已经描述了三个不同的由 HilD 领导的调节级联。在这里，通过分析 HilD 对沙门氏菌肠炎亚种（S. Typhimurium）中 yobH 基因的影响，我们进一步定义了由 HilD 介导的另一个调节级联，这是以前的全基因组分析所揭示的。在这个调节级联中，HilD 通过 SPI-1 中编码的 LuxR 样调节因子 SprB 来诱导毒力基因的表达。我们的数据表明，HilD 通过直接对抗 H-NS 对该基因上游启动子区域的抑制作用来诱导 sprB 的表达。然后，SprB 直接激活包括 yobH、slrP 和 ugtL 在内的几个基因的表达。有趣的是，我们发现 YobH 是一种只有 79 个氨基酸的蛋白质，是沙门氏菌侵入 HeLa 细胞和小鼠巨噬细胞所必需的。因此，我们的结果揭示了一种新型的沙门氏菌侵袭因子，并提供了更多证据支持 HilD-SprB 调节级联。
