Structural Chromosome Maintenance in Pseudomonas aeruginosa

描述(申请人提供)：铜绿假单胞菌是一种机会性的人类病原体，对免疫力受损的患者、烧伤患者和重症监护病房的患者构成严重威胁。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，从而增加细菌的适应性。它在介导感染中的作用仍然知之甚少。这项建议的重点是铜绿假单胞菌凝集素，它控制着其染色体的全球折叠。与典型的实验室菌株不同，铜绿假单胞菌编码几种特殊的凝集素，这些凝集素似乎在细胞生长过程中有差异表达。我们计划调查这一假说，即特殊凝集素的存在增加了铜绿假单胞菌的适合性。为此，我们打算表征铜绿假单胞菌凝集素的活性，并描述它们在不同生长条件下维持染色体的作用。这里的基本思想是，每种凝集素都经过优化，可以在自己的一组条件下发挥作用，它们的共同努力有助于铜绿假单胞菌在广泛的压力下生存下来。这些数据将有助于我们更好地理解病原菌和环境细菌中染色质维持的机制，以及它们在建立细菌病原体的高适合性和持久性方面的作用。 公共卫生相关性：这项建议探索了一种新的遗传因素的作用，该因素似乎有助于铜绿假单胞菌的高度适应性和持久性。了解这种联系的机制可能会为控制这种病原体引起的顽固性细菌感染提供新的方法。

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.