Mimetic sugar nucleotides to probe a strategic bacterial dehydrogenase enzyme

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This work will use exploratory scientific research to help further understand the way that the infectious bacterium and opportunistic pathogen, P. aeruginosa, regulates its own biosynthetic processes. Infections caused by P. aeruginosa are particularly harmful for sufferers of cystic fibrosis and one critical process that this bacterium utilises here is the production of a protective biofilm, which contributes to the ineffectiveness of standard antibiotic treatments used against it. Bacterial biofilm formation processes are governed by enzymes, which control the formation of key biological building blocks for assembly into the more complex, ultimate biofilm system. It is here that organic chemists can use their expertise to build new molecules to mimic the building blocks used by bacteria, effectively creating a molecular tool to investigate and understand a given enzyme mechanism in more detail. The molecular tools needed to do this are called sugar nucleotides and their construction is an intricate, exciting and diverse activity. Using such tools, important new information about enzyme structure and function can be collected, which could contribute towards instigating new approaches to disrupt specific enzyme activity and potentially arrest normal bacterial biofilm development. It is the purpose of this research to initiate an essential, molecular-level understanding of how a critical enzyme-controlled process operates within this pathogen.