Akbar Samina, Schechter Lisa M, Lostroh C Phoebe, Lee Catherine A
Department of Microbiology and Molecular Genetics, Harvard Medical School, 200 Longwood Avenue, Boston, MA 02115, USA.
Mol Microbiol. 2003 Feb;47(3):715-28. doi: 10.1046/j.1365-2958.2003.03322.x.
Salmonella typhimurium is a Gram-negative enteric pathogen that can infect intestinal epithelial cells and induce inflammation of the intestinal mucosa. These processes are mediated by a type III secretion system (TTSS), which is encoded on Salmonella pathogenicity island 1 (SPI1). Previous studies showed that four SPI1-encoded transcriptional regulators, HilD, HilC, HilA and InvF, act in an ordered fashion to co-ordinately activate expression of the SPI1 TTSS. HilD and HilC derepress hilA transcription. HilA activates invF as well as SPI1 genes that encode components of the TTS apparatus. InvF then activates genes that encode proteins secreted by the SPI1 TTS apparatus. In this scheme, HilD and HilC indirectly activate expression of the SPI1 TTS apparatus and its secreted substrates by affecting hilA expression. Here, we report that HilD and HilC can also activate expression of a subset of SPI1 genes independently of HilA. Our studies show that HilD and HilC activate transcription of invF from a promoter that is far upstream of its HilA-dependent promoter. This activation is most probably through direct binding of HilD and HilC to sequences upstream and downstream of this alternative HilA-independent promoter. We conclude that HilD and HilC have a second role in SPI1 gene regulation that is separate from their role in co-ordinating expression of the SPI1 TTSS through hilA.
鼠伤寒沙门氏菌是一种革兰氏阴性肠道病原体，可感染肠道上皮细胞并引发肠黏膜炎症。这些过程由Ⅲ型分泌系统（TTSS）介导，该系统由沙门氏菌致病岛1（SPI1）编码。先前的研究表明，四种由SPI1编码的转录调节因子HilD、HilC、HilA和InvF以有序方式协同激活SPI1 TTSS的表达。HilD和HilC解除对hilA转录的抑制。HilA激活invF以及编码TTS装置组件的SPI1基因。然后，InvF激活编码由SPI1 TTS装置分泌的蛋白质的基因。在此机制中，HilD和HilC通过影响hilA的表达间接激活SPI1 TTS装置及其分泌底物的表达。在此，我们报告HilD和HilC也可独立于HilA激活一部分SPI1基因的表达。我们的研究表明，HilD和HilC从其依赖HilA的启动子上游很远的一个启动子激活invF的转录。这种激活很可能是通过HilD和HilC直接结合到这个独立于HilA的替代启动子的上游和下游序列。我们得出结论，HilD和HilC在SPI1基因调控中具有第二个作用，这与其通过hilA协调SPI1 TTSS表达的作用是分开的。
