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

描述（由申请人提供）：铜绿假单胞菌是一种与大量感染相关的机会性病原体，影响全球数百万人。这种生物的一个重要毒力因素是产生氧化还原活性代谢物，称为非那嗪。苯胺类药物是一把双刃剑。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，它们会对宿主和相关微生物群落的成员造成氧化损伤。在我们对非那嗪的理解中，有一个很大的漏洞是铜绿假单胞菌是如何抵御它们的毒性作用的。这一建议将集中在了解铜绿假单胞菌如何调节非那嗪的浓度和氧化还原活性，以最大限度地提高适应性。我假设铜绿假单胞菌利用双重策略来处理这些代谢物，当它们的负面影响大于正面影响时：(I)

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.