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ROLE OF ALGB AND P AERUGINOSA ALGINATE GENE EXPRESSION

ROLE OF ALGB AND P AERUGINOSA ALGINATE GENE EXPRESSION
ALGB 和铜绿藻藻酸盐基因表达的作用
批准号:
2672286
负责人:
Daniel J Wozniak
金额:
$11.05万
依托单位:
依托单位国家:
美国
项目类别:
财政年份:
1994
资助国家:
美国
项目状态:
已结题
起止时间:
1994-09-01 至 1999-08-31

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中文摘要
翻译
大多数遗传性疾病囊性纤维化(CF)的患者 被粘液型铜绿假单胞菌定植和感染。 这些菌株是粘液状的,是由于一种多糖的过度生产。 称为藻酸盐,它在铜绿假单胞菌的发病机制中发挥作用 CF患者的肺组织。这种粘性聚合物会损害肺功能和 这使得几乎不可能从CF中根除这种微生物 呼吸道,使铜绿假单胞菌感染成为主要死亡原因 在慢性阻塞性肺疾病患者中。因此,这项建议的长期目标是 通过以下方法了解藻酸盐过量生产的分子基础 感染囊性纤维化患者的铜绿假单胞菌菌株。 藻酸盐生物合成基因由一个复杂的、多基因控制。 监管网络。这里提出的研究将集中在 藻酸盐调控蛋白A--藻酸盐调控蛋白 生物合成。为了理解这一点,有两个关键问题 构成这项提案的目标将得到解决。第一个目标是 以确定ALB的分子靶点。这将通过以下方式实现 DNA结合研究,藻类D的缺失分析,遗传特征 以及使用转录融合技术来 分离在ALB控制下的基因。这项提议的另一个目的是 确定algB转录激活的机制。特别是, 藻酸盐调节因子ALGT与DNA结合/弯曲的作用 蛋白质整合宿主因子在algB表达中的作用将被研究。 对这些蛋白作出反应的algB启动子(S)的特征是 核糖核酸酶保护图谱及引物延伸分析。 生物化学和遗传方法的结合在这些 研究应该为这一复杂的监管提供洞察力 重要的毒力因素,最终目标是改善 Lite适用于带藻酸盐产生菌的CF患者。 铜绿假单胞菌。
英文摘要
Most patients with the genetic disease cystic fibrosis (CF) become colonized and infected with mucoid strains of Pseudomonas aeruginosa. These strains are mucoid due to the overproduction of a polysaccharide called alginate, which plays a role in the pathogenesis of P. aeruginosa in the lungs of CF patients. This viscous polymer impairs lung function and makes it almost impossible to eradicate the organism from the CF respiratory tract, making P. aeruginosa infections the major cause of death in CF patients. Therefore, the long-term objective of this proposal is to understand the molecular basis for the overproduction of alginate by strains of P. aeruginosa which infect cystic fibrosis patients. The alginate biosynthetic genes are controlled by a complex, multigenic regulatory network. The research proposed here will focus on the role of a AlgB, a key alginate regulatory protein, in the control of alginate biosynthesis. In order to understand this, two critical questions which constitute the aims of this proposal will be addressed. The first goal is to identify the molecular targets of AlgB. This will be accomplished by DNA binding studies, a deletion analysis of algD, genetic characterization of algB suppressor strains, and the use of transcriptional fusions to isolate genes under AlgB control. Another aim of this proposal is to determine the mechanism of algB transcriptional activation. In particular, the roles of the alginate regulator AlgT and the DNA binding/bending protein integration host factor in algB expression will be investigated. The algB promoter(s) responsive to these proteins will be characterized by ribonuclease protection mapping and primerextension analysis. The combination of biochemical and genetic approaches utilized in these studies should provide insights into the complex regulation of this important virulence factor with the ultimate goal of an improved quality of lite for CF patients colonized with alginate-producing strains of P. aeruginosa.
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The impact of bacteriophage therapy on wound infection dynamics
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  • 财政年份:
    2022
  • 负责人:
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  • 依托单位:
The impact of bacteriophage therapy on wound infection dynamics
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Revisiting alginate paradigms
  • 批准号:
    10294953
  • 项目类别:
  • 资助金额:
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  • 财政年份:
    2017
  • 负责人:
    Daniel J Wozniak
  • 依托单位:
Revisiting alginate paradigms
  • 批准号:
    10054154
  • 项目类别:
  • 资助金额:
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  • 财政年份:
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