Amphiphilic Siderophores: Biosynthesis, Iron Uptake and Effect on Microbial Growth

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Nearly all bacteria require iron to grow. Understanding the process by which bacteria obtain iron from their surroundings provides valuable insight into how to disrupt the iron uptake process, and suggests potential new strategies to limit growth of deleterious microbes. The focus of this proposal is to find out how unique compounds called siderophores are produced for iron uptake in Vibrio harveyi and other microbes for which their production is tied to bacterial colony formation and survival. Siderophores are natural materials produced by bacteria that bind iron(III) very tightly playing a vital role in iron uptake by the bacterium. Through these investigations, graduate students will be trained in the application of a broad spectrum of modern techniques to a multidisciplinary research program. The graduate students will, in turn, also gain valuable experience as mentors to undergraduate researchers in the laboratory, and undergraduates will gain hands-on research experience.With this award, the Chemistry of Life Processes Program in the Chemistry Division is funding Alison Butler from the University of California, Santa Barbara to investigate the biosynthesis of key amphiphilic siderophores, such as the amphi-enterobactins, to investigate their physical properties including the ferric stability constants and membrane partitioning constants for different forms of the amphi-enterobactins, to investigate key esterases and outer membrane receptor proteins present in the genome of V. harveyi which are suspected to be important in the mechanism of iron uptake, as well as to investigate other key amphiphilic siderophores. V. harveyi is the widely studied model organism for quorum sensing, the process by which bacteria sense cell density. Discoveries from these investigations will provide new insights into the importance of the fatty acid in acylated siderophores in the iron uptake process.