Elucidation of the biosynthesis of 4-hydroxy-2-alkylquinolines by pseudomonas aeruginosa

铜绿假单胞菌生物合成 4-羟基-2-烷基喹啉的阐明

• 批准号: 38364-2007
• 负责人: Lépine, François
• 金额: $ 2.19万
• 依托单位: Institut national de la recherche scientifique
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2007
• 资助国家: 加拿大
• 起止时间: 2007-01-01 至 2008-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=362554
• 关键词: Elucidation; biosynthesis; hydroxy; alkylquinolines; pseudomonas

In recent years it has been demonstrated that bacteria communicate with one another, in a process called « Quorum Sensing ». In this mechanism, bacteria secrete one or many signalling molecules which, when they have reched a specific concentration in the medium, bind to their corresponding regulator protein that will increase the production of the signalling compounds and will also activate other virulence genes. During the early stage of an infection, the advantage of such synchronized behaviour is to wait until the number of bacteria is sufficiently large so that the simultaneous release of virulence factor could overwhelm the host defence.In this study, we want to characterize the enzymatic systems involved in the biosynthesis of one new family of signalling molecules called 4-hydroxy-2-alkylquinolines (HAQs). These compounds are signalling molecules produced by Pseudomonas aeruginosa , an opportunistic pathogen responsible for most fatalities for people afflicted with cystic fibrosis. The objective of the work is to isolate the enzymes responsible for HAQ synthesis in order to better understand how they function and eventually find specific inhibitors of these enzymes. By preventing the synthesis of these compounds, we believe we could inhibit part of the quorum sensing mechanism in this bacterium, and thus reduce its pathogenicity. Inhibiting bacterial virulence is another way to prevent an infection, leaving to the host natural defence the role of eliminating a bacteria rendered less virulent. This approach is likely to be less prone to the development of resistance, a problem that pleagues the use of antibiotics which target bacterial viability rather than virulence.

近年来，已经证明细菌在一个称为“群体感应”的过程中相互交流。在这种机制中，细菌分泌一种或多种信号分子，当它们在培养基中达到特定浓度时，与它们相应的调节蛋白结合，这将增加信号化合物的产生，并且还将激活其他毒力基因。在感染的早期阶段，这样的同步行为的优点是等到细菌的数量是足够大，使毒力因子的同时释放可能压倒宿主defens.In这项研究中，我们要描述的酶系统参与的一个新的家庭的信号分子称为4-羟基-2-烷基喹啉（HAQs）的生物合成。这些化合物是由铜绿假单胞菌产生的信号分子，铜绿假单胞菌是一种机会致病菌，对患有囊性纤维化的人的大多数死亡负责。这项工作的目的是分离负责HAQ合成的酶，以便更好地了解它们的功能，并最终找到这些酶的特异性抑制剂。通过阻止这些化合物的合成，我们相信我们可以抑制这种细菌的部分群体感应机制，从而降低其致病性。抑制细菌毒力是防止感染的另一种方法，将消除毒性较低的细菌的作用留给宿主的自然防御。这种方法可能不太容易产生耐药性，这是一个困扰使用针对细菌活力而不是毒力的抗生素的问题。