Pseudomonas aeruginosa Genomic Islands and Virulence

铜绿假单胞菌基因组岛和毒力

基本信息

批准号：
7752565
负责人：
ALAN R HAUSER
金额：
$ 33.97万
依托单位：
NORTHWESTERN UNIVERSITY AT CHICAGO
依托单位国家：
美国
项目类别：
财政年份：
2008
资助国家：
美国
起止时间：
2008-12-22 至 2013-11-30
项目状态：
已结题

项目摘要

DESCRIPTION (provided by applicant): P. aeruginosa strains differ from one to another in their ability to cause severe disease, in both animals and plants. Since about 90% of P. aeruginosa ORFs, including a large number that encode virulence factors, make up a core set of genes that are conserved throughout all strains, it is likely that a proportion of the phenotypic heterogeneity of P. aeruginosa is attributable to large strain-specific genomic islands that were acquired through horizontal transfer. These genomic islands represent a wealth of genetic information that remains relatively unexplored. Although some genomic islands have been associated with virulence in various models (and therefore are classified as pathogenicity islands), the full impact of variable genomic islands on the virulence of P. aeruginosa has yet to be examined. We hypothesize that genomic islands present in some strains but absent in others account for some of the heterogeneity in virulence of P. aeruginosa strains and that characterization of these genomic islands will result in the identification of novel virulence determinants. The goals of this proposal are two-fold: first, a substantial number of novel genomic islands will be identified and characterized, adding to the database of genetic information known to be carried by this bacterium and furthering our understanding of the evolution of these genetic elements. Second, genomic islands that contribute to the overall virulence of P. aeruginosa will be identified, as will their individual ORFs that account for this phenotype. The general strategy of this proposal is to exploit the differences in virulence between P. aeruginosa strains to identify strains with a high likelihood of containing large amounts of variable genetic information in the form of novel genomic islands. These strains will be targeted for in-depth analysis. Genomic islands in these strains will be sequenced, and those that contribute to virulence will be identified. Finally, mutational analyses will be performed to identify the ORFs harbored by these islands that are responsible for the enhanced virulence. Successful completion of this proposal will yield a wealth of information regarding the content and characteristics of P. aeruginosa genomic islands and will identify novel virulence factors. Clinically, the identification of genomic islands that impact the disease-causing potential of P. aeruginosa strains is of potential prognostic and therapeutic importance. PUBLIC HEALTH RELEVANCE: bacterium Pseudomonas aeruginosa is one of the most frequent causes of pneumonia acquired in the hospital, a disease that has a mortality rate of 30-60%. Our overall objective is to better understand why some strains of P. aeruginosa cause more severe disease than other strains. This information could lead to prognostic, diagnostic, and therapeutic advances.

描述（由申请人提供）：铜绿假单胞菌菌株在动物和植物中引起严重疾病的能力在另一个方面不同。由于大约90％的铜绿假单胞菌ORF（包括编码毒力因子的大量数量）构成了在所有菌株中保守的一组核心基因，因此铜绿假单胞菌的表型异质性的一部分很可能归因于大型菌株特异性基因组群岛，这些基因组基因组群岛可通过水平转移获得。这些基因组岛代表了许多遗传信息，这些信息仍然相对尚未探索。尽管某些基因组岛与各种模型中的毒力有关（因此被归类为致病岛），但可变基因组岛对铜绿假单胞菌毒力的全部影响尚未进行研究。我们假设存在一些菌株中存在的基因组岛，但在另一些菌株中缺乏占铜绿假单胞菌菌株毒力的某些异质性，并且这些基因组岛的表征将导致鉴定出新的毒力确定性。该提案的目标是两个方面：首先，将确定和表征大量的新型基因组岛屿，这增加了已知的遗传信息数据库，并进一步发展了我们对这些遗传元素进化的理解。其次，将确定有助于铜绿假单胞菌的总体毒力的基因组岛，以及解释这种表型的单个ORF。该提议的一般策略是利用铜绿假单胞菌菌株之间的毒力差异，以鉴定具有很可能以新型基因组岛形式含有大量可变遗传信息的菌株。这些菌株将被针对深入分析。这些菌株中的基因组岛将进行测序，并确定那些有助于毒力的岛屿。最后，将进行突变分析，以识别这些岛屿所包含的ORF，这些ORF负责增强的毒力。该提案的成功完成将产生有关铜绿假单胞菌基因组岛的内容和特征的大量信息，并将确定新颖的毒力因素。在临床上，影响铜绿假单胞菌菌株引起疾病潜力的基因组岛的鉴定具有潜在的预后和治疗意义。公共卫生相关性：铜绿细菌是医院中最常见的肺炎原因之一，这种疾病的死亡率为30-60％。我们的总体目标是更好地理解为什么某些铜绿假单胞菌菌株比其他菌株更严重。这些信息可能会导致预后，诊断和治疗性进步。