GENETIC REGULATION OF THE TWIN ARGININE TRANSLOCATION SYSTEM IN SALMONELLA ENTERICA SEROVAR TYPHIMURIUM

项目摘要 沙门氏菌引起一系列疾病，从自限性胃肠炎到危及生命的全身性疾病。 感染，在各种宿主中。疾控中心估计，非伤寒沙门氏菌导致120万人死亡 仅在美国，每年就有450人死于食源性疾病。肠沙门氏菌血清型 鼠伤寒杆菌是全球引起胃肠炎的主要原因之一，在#年被用作人类伤寒的模型。 老鼠。双胞胎精氨酸转位系统(TAT)是一种在细菌中保守的蛋白质分泌系统， 古生菌和植物。 在革兰氏阴性细菌中，底物蛋白从细胞质输出到周质是必需的。 有机体的。TAT衬底通常在出口到周质之前必须正确折叠。在沙门氏菌中， 大约有30种蛋白质是TAT的底物，其中包括氢酶和酰胺酶。而当 多项研究表明，tat是沙门氏菌和其他细菌致病所必需的。 病原体，没有发表的研究表明对该系统的调节，talABC被认为是结构性的 表达。我们已经证明，增加胆汁浓度会诱导一种atabc-lacZ的表达 核聚变。在培养基中加入9%的胆盐，可获得约3倍的Tabc-LacZ。我们还发现， 与野生型相比，tatabc的缺失对靶向抗生素的肽聚糖更敏感，尽管添加了 氨苄西林不能激活atabc-lacZ的表达。这些发现引出了几个问题： TAT表达激活胆汁的机制？哪些启动子元件对基因的表达很重要 塔塔ABC？

Project Summary Salmonella species cause a range of diseases, from self-limiting gastroenteritis to life-threatening systemic infections, in a variety of hosts. The CDC estimates that non-typhoid Salmonella species cause 1.2 million cases of foodborne illness and 450 deaths per year in the United States alone. Salmonella enterica serovar Typhimurium is a leading cause of gastroenteritis worldwide and is used as a model for human typhoid fever in mice. The twin arginine translocation system (Tat) is a protein secretion system that is conserved in bacteria, archaea, and plants. In gram-negative bacteria, it is required for the export of substrate proteins from the cytoplasm to the periplasm of the organism. Tat substrates typically must be properly folded prior to export to the periplasm. In Salmonella, there are about 30 proteins that are substrates of Tat, among these are hydrogenases and amidases. While several studies have demonstrated that Tat is required for virulence in Salmonella and other bacterial pathogens, no published work has shown regulation of the system and tatABC is thought to be constitutively expressed. We have demonstrated that increasing concentrations of bile induce expression of a tatABC-lacZ fusion. Addition of 9% bile salt to LB media induces tatABC-lacZ about three-fold. We also have found that deletions of tatABC are more sensitive than wild type to peptidoglycan targeting antibiotics, though the addition of ampicillin does not activate expression of tatABC-lacZ. These finding leads to several questions: What is the mechanism of bile activation of tat expression? What promoter elements are important for expression of tatABC?