Structural Chromosome Maintenance in Pseudomonas aeruginosa

描述（由申请人提供）：铜绿假单胞菌是一种机会性人类病原体，对免疫力受损患者、烧伤患者和重症监护病房患者构成严重威胁。铜绿假单胞菌的高致病性在很大程度上取决于其在恶劣环境中的生存能力。染色质结构是控制细菌适应环境变化的主要因素，从而提高细菌的适应性。它在介导感染中的作用仍然知之甚少。这一建议的重点是铜绿假单胞菌凝聚，控制其染色体的整体折叠。与原型实验室菌株相比，铜绿假单胞菌编码几种特化凝聚蛋白，这些凝聚蛋白在细胞生长过程中似乎是差异表达的。我们计划调查的假设，专门的凝缩蛋白的存在增加假铜绿假单胞菌的适应度。为此，我们打算表征铜绿假单胞菌凝聚蛋白的活性，并描述它们在不同生长条件下染色体维持中的作用。这里的基本思想是，每一种凝缩蛋白都是在自己的一组条件下进行优化的，并且它们的共同作用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的染色质维持机制及其在细菌病原体高适应性和持久性中的作用。

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.