ALGINATE GENE REGULATION AND INFECTION IN INFECTION IN C

铜绿假单胞菌导致严重和衰弱的肺 患有囊性纤维化的儿童和年轻人的感染 （CF）。 从CF患者呼吸道分离的铜绿假单胞菌 从非粘液形式转换为粘液，产生藻酸盐的形式， 疾病的进展。 藻酸盐包封被认为 保护感染细胞免受吞噬作用和抗生素 疗法 抑制这种保护性藻酸盐屏障的合成 可能使铜绿假单胞菌对抗生素治疗更敏感， 宿主免疫系统，从而减轻并发症， P.囊性纤维化患者的铜绿假单胞菌感染。 已经 证明了海藻酸盐的合成是由独特的 CF患者的肺部环境，包括高电解质 浓度和脱水粘液。 已经证明，两个 与藻酸盐合成有关的重要基因algC和algD， 调节蛋白AlgR 1和AlgR 2的共同控制，它们属于 属于双组分细菌信号转导家族。 拟议 研究的目的是阐明控制 海藻酸合成基因的表达。 具体来说，角色 AlgR 1在调节algC和algD启动子中的作用， 将研究磷酸化的机制。 此外，如何 受CF折磨的肺所特有的环境信号被转导， 将研究AlgR 2的自磷酸化。 理解 藻酸盐基因激活的各种步骤可允许非- 毒性抑制剂，并可能导致有效的治疗 从CF肺中根除铜绿假单胞菌的方案。

Pseudomonas aeruginosa causes severe and debilitating pulmonary infections in children and young adults afflicted with cystic fibrosis (CF). P. aeruginosa isolated from the respiratory tract of CF patients switches from a non-mucoid form to a mucoid, alginate producing form upon progression of the disease. Alginate encapsulation is believed to protect the infecting cells from phagocytosis as well as from antibiotic therapy. Inhibition of the synthesis of this protective alginate barrier may render P. aeruginosa more susceptible to antibiotic therapy and the host immune system, thereby alleviating the complications that arise from P. aeruginosa infections in cystic fibrosis patients. It has been demonstrated that alginate synthesis is triggered by the unique environment in the lungs of CF patients which includes high electrolyte concentrations and a dehydrated mucus. It has been shown that two important genes involved in alginate synthesis, algC and algD, are under the common control of regulatory proteins AlgR1 and AlgR2, which belong to the two-component bacterial signal transduction family. The proposed research is aimed at elucidating the regulatory mechanisms that control the expression of alginate biosynthesis genes. Specifically, the role of AlgR1 in regulation of algC and algD promoters and the detailed mechanisms of phosphorylation will be studied. Furthermore, how environmental signals unique to CF-afflicted lungs are transduced to AlgR2 for its autophosphorylation will be investigated. Understanding various steps in alginate gene activation may allow development of non- toxic inhibitors for this process, and may lead to an effective treatment regimen for the eradication of P. aeruginosa from the CF lung.