Schechter L M, Lee C A
Department of Microbiology and Molecular Genetics, Harvard Medical School, 200 Longwood Avenue, Boston, MA 02115, USA.
Mol Microbiol. 2001 Jun;40(6):1289-99. doi: 10.1046/j.1365-2958.2001.02462.x.
During infection, Salmonella enterica serovar Typhimurium colonizes the small intestine of its hosts. This process requires a type III secretion system encoded by several genes on Salmonella pathogenicity island 1 (SPI1), a 40 kb region of DNA near centisome 63 of the Salmonella chromosome. SPI1 gene expression is controlled by a complex regulatory cascade. HilA, a member of the OmpR/ToxR family of transcriptional regulators, directly activates the expression of two SPI1 operons encoding type III apparatus components. hilA transcription is repressed by many environmental conditions and regulatory mutations. This repression requires an upstream repressing sequence (URS) located between -314 and -68 relative to the hilA transcription start site. The repressing activity of the URS is counteracted by two AraC/XylS family members named HilC and HilD. We show that HilC and HilD bind directly to the hilA promoter region in vitro. We also provide evidence that HilC and HilD bind to the same or overlapping sites within the URS. Our data are consistent with a model in which HilC and HilD derepress hilA expression by binding directly to the URS and counteracting its repressing effect in vivo.
在感染过程中，鼠伤寒沙门氏菌血清型鼠伤寒沙门氏菌定殖于宿主的小肠。这一过程需要由沙门氏菌致病岛1（SPI1）上的几个基因编码的III型分泌系统，SPI1是沙门氏菌染色体63分摩附近的一个40 kb的DNA区域。SPI1基因的表达受一个复杂的调控级联控制。HilA是转录调节因子OmpR/ToxR家族的成员，直接激活两个编码III型装置组件的SPI1操纵子的表达。hilA转录受到许多环境条件和调控突变的抑制。这种抑制需要一个位于相对于hilA转录起始位点-314至-68之间的上游抑制序列（URS）。URS的抑制活性被两个名为HilC和HilD的AraC/XylS家族成员抵消。我们表明，HilC和HilD在体外直接结合hilA启动子区域。我们还提供证据表明，HilC和HilD结合到URS内的相同或重叠位点。我们的数据与一个模型一致，即HilC和HilD通过直接结合URS并在体内抵消其抑制作用来解除对hilA表达的抑制。
