Departamento de Microbiología Molecular, Instituto de Biotecnología, Universidad Nacional Autónoma de México, Cuernavaca, Morelos, Mexico.
Unidad de Investigación en Medicina Experimental, Facultad de Medicina, Universidad Nacional Autónoma de México, Mexico City, Mexico.
J Bacteriol. 2022 May 17;204(5):e0058521. doi: 10.1128/jb.00585-21. Epub 2022 Apr 11.
One important event for the divergence of Salmonella from Escherichia coli was the acquisition by horizontal transfer of the almonella athogenicity sland 1 (SPI-1), containing genes required for the invasion of host cells by Salmonella. HilD is an AraC-like transcriptional regulator in SPI-1 that induces the expression of the SPI-1 and many other acquired virulence genes located in other genomic regions of Salmonella. Additionally, HilD has been shown to positively control the expression of some ancestral genes (also present in E. coli and other bacteria), including . In this study, we determined that both the gain of HilD and -regulatory evolution led to the integration of the gene into the HilD regulon. Our results indicate that a HilD-binding sequence was generated in the regulatory region of the S. enterica serovar Typhimurium gene, which mediates the activation of promoter 1 of this gene under SPI-1-inducing conditions. Furthermore, we found that repression by H-NS, a histone-like protein, was also adapted on the S. Typhimurium gene and that HilD activates the expression of this gene in part by antagonizing H-NS. Additionally, our results revealed that the expression of the S. Typhmurium gene is also activated in response to low phosphate but independently of the PhoB/R two-component system, known to regulate the E. coli gene in response to low phosphate. Thus, our results indicate that -regulatory evolution has played a role in the expansion of the HilD regulon and illustrate the phenomenon of differential regulation of ortholog genes. Two mechanisms mediating differentiation of bacteria are well known: acquisition of genes by horizontal transfer events and mutations in coding DNA sequences. In this study, we found that the ancestral gene is differentially regulated between Salmonella Typhimurium and Escherichia coli, two closely related bacterial species. Our results indicate that this differential regulation was generated by mutations in the regulatory sequence of the S. Typhimurium gene and by the acquisition by S. Typhimurium of foreign DNA encoding the transcriptional regulator HilD. Thus, our results, together with those from an increasing number of studies, indicate that -regulatory evolution can lead to the rewiring and reprogramming of transcriptional regulation, which also plays an important role in the divergence of bacteria through time.
沙门氏菌与大肠杆菌分化的一个重要事件是通过水平转移获得了沙门氏菌致病性岛 1（SPI-1），其中包含沙门氏菌入侵宿主细胞所需的基因。HilD 是 SPI-1 中的一个 AraC 样转录调节因子，它诱导 SPI-1 和许多其他位于沙门氏菌其他基因组区域的获得性毒力基因的表达。此外，HilD 已被证明正向控制一些祖先基因（也存在于大肠杆菌和其他细菌中）的表达，包括 。在这项研究中，我们确定 HilD 的获得和 -调控进化导致了 基因整合到 HilD 调控子中。我们的结果表明，在 S. enterica 血清型 Typhimurium 的 基因调控区域中产生了一个 HilD 结合序列，该序列介导了该基因在 SPI-1 诱导条件下启动子 1 的激活。此外，我们发现组蛋白样蛋白 H-NS 的抑制作用也适应了 S. Typhimurium 基因，HilD 通过拮抗 H-NS 部分激活了该基因的表达。此外，我们的结果表明，S. Typhmurium 基因的表达也响应低磷酸盐而被激活，但不依赖于已知响应低磷酸盐调节大肠杆菌 基因的 PhoB/R 双组分系统。因此，我们的结果表明，-调控进化在 HilD 调控子的扩展中发挥了作用，并说明了同源基因差异调控的现象。 介导细菌分化的两种机制是众所周知的：通过水平转移事件获得基因和编码 DNA 序列的突变。在这项研究中，我们发现两个密切相关的细菌物种沙门氏菌 Typhimurium 和大肠杆菌中，祖先基因的表达存在差异。我们的结果表明，这种差异调控是由 S. Typhimurium 基因调控序列的突变和 S. Typhimurium 获得编码转录调节因子 HilD 的外源 DNA 引起的。因此，我们的结果与越来越多的研究结果一起表明，-调控进化可以导致转录调控的重新布线和重新编程，这在细菌随时间的分化中也起着重要作用。
