Structural Variants of AI-2 Analogs to Probe Quorum Sensing in Diverse Bacteria
Gamby, Sonja Josette
Sintim, Herman O.
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Bacterial infections which were once easily managed with antibiotics are now reemerging as a serious threat to human health. The difficulty in managing infectious diseases is arising out of bacterial resistance to front line antibiotics. A new paradigm for fighting bacterial infection via the inhibition of quorum sensing has emerged. Quorum sensing is the process by which small diffusible molecules (autoinducers) are used to sense population density and upregulate genes. Notably, genes for virulence production and biofilm formation have been found to be controlled by this process. Thus, quorum sensing, offers an alternative target for the treatment of bacterial infections. One autoinducer which has been identified across many bacterial species is AI-2. The goals of this thesis were to make more hydrolytically stable analogs of AI-2 as potent inhibitors of quorum sensing, as well as, exploring the effects of AI-2 analogs on QS in P. aeruginosa. In this study, the processing of bis ester protected AI-2 analogs was examined. Also, two long chain AI-2 analogs were synthesized and tested for their ability to inhibit QS in P.aeruginosa. It was found that bis protected analogs are processed different across bacterial species. Also, long chain AI-2 analogs were found to be inhibitors of QS in P. aeruginosa, specifically, by inhibiting a LasR receptor which typically responds to a different class of autoinducer.