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

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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.