Structural Chromosome Maintenance in Pseudomonas aeruginosa

描述（由申请方提供）：铜绿假单胞菌是一种人类机会致病菌，对免疫力受损患者、烧伤患者和重症监护室患者构成严重威胁。铜绿假单胞菌的高致病效率在很大程度上在于其在恶劣环境中生存的能力。染色质结构是控制细菌适应环境变化的主要因素，从而增加细菌的适应性。它在介导感染中的作用仍然知之甚少。该提议集中于铜绿假单胞菌凝聚素，其控制其染色体的整体折叠。与原型实验室菌株相反，铜绿假单胞菌编码几种在细胞生长期间似乎差异表达的特化凝聚素。我们计划调查的假设，专门的凝聚素的存在下，增加适应性的铜绿假单胞菌。为此，我们打算表征铜绿假单胞菌凝聚素的活性，并描绘它们在各种生长条件下在染色体维持中的作用。这里的基本思想是，每种凝聚素都被优化以在自己的条件下发挥作用，并且将它们的努力结合起来有助于铜绿假单胞菌在广泛的压力下生存。这些数据将有助于我们更好地了解致病菌和环境细菌中染色质维持的机制及其在建立细菌病原体的高适应性和持久性中的作用。 公共卫生相关性：该提议探讨了一种新的遗传因子的作用，该遗传因子似乎有助于铜绿假单胞菌的高适应性和持久性。了解这种联系的机制可能会提出新的方法来控制由这种病原体引起的寄生细菌感染。

DESCRIPTION (provided by applicant): Pseudomonas aeruginosa is an opportunistic human pathogen, which presents a serious threat to patients with impaired immunity, burn victims and in intense care units. The high pathogenic efficiency of P. aeruginosa resides, to large extent, in its ability to survive in hostile environment. Chromatin structure is a major factor that governs bacterial adaptation to environmental changes and thereby increases fitness of bacteria. Its role in mediating infection is still poorly understood. This proposal focuses on the P. aeruginosa condensins, which control the global folding of its chromosome. In contrast to archetypal laboratory strains, P. aeruginosa encodes several specialized condensins which appear to be differentially expressed during cell growth. We plan to investigate the hypothesis that the presence of specialized condensins increases fitness of P. aeruginosa. To this end, we intend to characterize the activity of the P. aeruginosa condensins and delineate their roles in chromosome maintenance under various growth conditions. The underlying idea here is that each condensin is optimized to act under its own set of conditions, and combining their efforts helps P. aeruginosa to survive a broad range of stresses. These data will help us better understand the mechanisms of chromatin maintenance in pathogenic and environmental bacteria and their role in establishing high fitness and persistence of bacterial pathogens. PUBLIC HEALTH RELEVANCE: This proposal explores the role of a novel genetic factor that appears to contribute to high fitness and persistence of Pseudomonas aeruginosa. Understanding the mechanism of this link might suggest novel ways to control recalcitrant bacterial infections caused by this pathogen.