Studies on the Pseudomonas aeruginosa cell-to-cell signal PQS

描述(申请人提供)：铜绿假单胞菌约占美国医院获得性感染的10%，在大多数囊性纤维化患者中会导致慢性、衰弱的肺部感染。增加这些感染的重要性的是，这种微生物能够迅速对许多抗生素产生抗药性，这大大限制了治疗选择。尽管多年来对新的抗菌疗法的需求一直很迫切，但开发有用的新抗生素一直很困难。一项前景看好的研究集中在细菌用来控制包括毒力在内的许多功能的细胞间信号系统。铜绿假单胞菌使用三种不同的细胞间信号系统来协调基因的表达，本提案的主题是信号2-庚基-3-羟基-4-喹诺酮[称为假单胞菌喹诺酮信号(PQS)]。PQS是植物、昆虫和动物致病所必需的，在感染铜绿假单胞菌的囊性纤维化患者的肺中产生。我们的计划是完成实验，帮助我们更好地理解PQS在铜绿假单胞菌细胞间信号传递和毒力中的重要性。我们建议进行有针对性的实验，以解决PQS如何激活基因，以及其合成背后的机制。这项研究的长期目标是开发干扰PQS信号的方法。我们相信，PQS信号系统及其正常功能所需的组件将提供靶点，作为未来治疗干预的靶点，从而降低铜绿假单胞菌的毒力。

DESCRIPTION (provided by applicant): Pseudomonas aeruginosa is responsible for approximately 10% of the hospital-acquired infections in the U.S., and causes a chronic, debilitating lung infection in most cystic fibrosis patients. Adding to the significance of these infections is the fact that this organism is capable of rapidly developing resistance to many antibiotics, which significantly limits treatment options. While the need for novel antimicrobial treatments has been pressing for years, the development of useful new antibiotics has been difficult. One promising line of research has centered on the cell-to-cell signaling systems used by bacteria to control many functions, including virulence. P. aeruginosa uses three different intercellular signaling systems to coordinate gene expression and the topic of this proposal is the signal 2-heptyl-3-hydroxy-4-quinolone [referred to as the Pseudomonas Quinolone Signal (PQS)]. PQS is required for virulence in plants, insects, and animals and is produced in the lungs of cystic fibrosis patients who are infected by P. aeruginosa. Our plan is to complete experiments that will help us to better understand the significance of PQS in P. aeruginosa cell-to-cell signaling and virulence. We propose focused experiments that will address how PQS activates genes, and the mechanisms behind its synthesis. The long term goal of this research is to develop methods that interfere with PQS signaling. We believe that the PQS signaling system and the components required for its proper function will provide targets at which to aim future therapeutic interventions that will decrease P. aeruginosa virulence.