Defensive strategies against the toxic effects of self-produced phenazine metabol

描述(申请人提供)：铜绿假单胞菌是一种与影响全球数百万人的大量感染有关的机会性病原体。对这种生物来说，一个重要的毒力因素是氧化还原活性代谢物吩嗪的产生。奋乃静是一把双刃剑。一方面，它们对生产者的生存起着重要的生理作用；另一方面，它们可以对宿主和相关微生物群落的成员造成氧化损伤。我们对吩嗪类药物的理解有一个很大的漏洞，那就是铜绿假单胞菌是如何防御它们的毒性作用的。这项建议将侧重于了解铜绿假单胞菌如何调节吩嗪类药物的浓度和氧化还原活性，以最大限度地提高健康水平。我假设，当这些代谢物的负面影响大于正面影响时，铜绿假单胞菌使用双重策略来处理它们：(I) 与环境隔离和屏蔽；(Ii)主动降解。从这项工作中获得的见解将有助于我们了解这种重要的人类病原体的体内生理学，并将影响我们在感染期间对铜绿假单胞菌的思考和反应。

DESCRIPTION (provided by applicant): Pseudomonas aeruginosa is an opportunistic pathogen associated with a large number of infections that impact millions worldwide. One important virulence factor for this organism is the production of redox-active metabolites called phenazines. Phenazines are a double-edged sword. While on the one hand, they play important physiological roles in the survival of their producers; on the other, they can cause oxidative damage to both the host and members of the associated microbial community. A large hole in our understanding of phenazines is how P. aeruginosa defends itself against their toxic effects. This proposal will focus on understanding how P. aeruginosa modulates the concentration and redox activity of phenazines to maximize fitness. I hypothesize that P. aeruginosa utilizes a two-fold strategy to deal with these metabolites when their negative effects outweigh the positive: (i) sequestration and shielding from the environment and (ii) active degradation. Insights gained from this work will help us to understand the in vivo physiology of this important human pathogen, and will influence how we think about and respond to P. aeruginosa during infection.