Hha is a negative modulator of transcription of hilA, the Salmonella enterica serovar Typhimurium invasion gene transcriptional activator
Hha is a negative modulator of transcription of hilA, the Salmonella enterica serovar Typhimurium invasion gene transcriptional activator
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DOI：
10.1128/jb.183.22.6620-6629.2001
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发表时间：
2001-11-01
影响因子：
3.2
通讯作者：
Jones, BD
中科院分区：
文献类型：
--
作者：
Fahlen, TF;Wilson, RL;Jones, BD
建立肠道沙门氏菌鼠伤寒血清型小鼠感染的早期步骤是小肠的肠粘膜渗透。沙门氏菌侵袭表型的大部分基因编码的沙门氏菌致病岛1，其转录控制的hilA转录激活因子。hilA的表达受包括氧、渗透压、pH和生长期的环境信号调节，使得任何一种次优条件的存在导致hilA表达的抑制和侵袭性表型。我们通过将鼠伤寒沙门氏菌染色体DNA基因库引入鼠伤寒沙门氏菌hil4：：Tn5lacZY报告菌株中来寻找hilA的负调控因子。该筛选已经鉴定出hha基因作为对hil4表达施加负面影响的调节器。质粒编码的hha显著降低hilA：：Tn5lacZY染色体表达，以及侵袭基因invF、prgH和sipC的表达。hha无效突变导致染色体编码和质粒编码的hilA：：Tn5lacZY表达的实质性去阻遏。将质粒编码的hha引入菌株SL 1344中导致使用体外和体内测定的侵袭减弱。重要的是，纯化的Hha蛋白被发现结合到一个hilA DNA启动子片段，表明Hha蛋白的调节活性发生在hilA启动子。这些数据为沙门氏菌入侵基因调控的发展模型增加了细节。
An early step in the establishment of Salmonella enterica serovar Typhimurium murine infection is the penetration of the intestinal mucosa of the small intestine. The majority of the genes responsible for the Salmonella invasive phenotype are encoded on Salmonella pathogenicity island 1, and their transcription is controlled by the hilA transcriptional activator. The expression of hilA is regulated by environmental signals including oxygen, osmolarity, pH, and growth phase such that the presence of any one suboptimal condition results in repression of hilA expression and the invasive phenotype. We have conducted a search for negative regulators of hilA by introduction of a Salmonella enterica serovar Typhimurium chromosomal DNA gene bank into a Salmonella enterica serovar Typhimurium hil4::Tn5lacZY reporter strain. This screen has identified the hha gene as a regulator that exerts a negative influence on hil4 expression. Plasmid-encoded hha significantly reduces hilA::Tn5lacZY chromosomal expression, as well as expression of the invasion genes invF, prgH, and sipC. An hha null mutation results in substantial derepression of both chromosomally encoded and plasmid-encoded hilA::Tn5lacZY expression. Introduction of plasmid-encoded hha into strain SL1344 results in attenuation of invasion using in vitro and in vivo assays. Importantly, purified Hha protein was found to bind to a hilA DNA promoter fragment, suggesting that the regulatory activity of the Hha protein occurs at the hilA promoter. These data add detail to the developing model of the regulation of Salmonella invasion genes.