With this award, the Chemistry of Life Processes Program in the Chemistry Division is funding Dr. Timothy Wencewicz from Washington University in St. Louis to investigate iron acquisition in bacterial communities. Iron is an essential element in numerous life processes. Bacteria obtain iron directly from their environment, like soils, the oceans, and host organisms. Bacteria make and excrete compounds called siderophores to capture or "chelate" iron. The metal becomes a cargo in the siderophore transporter, and together they are taken up by the bacterium that made the siderophore in the first place. This research aims to understand the chemical principles that enable siderophores to function in complex cellular environments. The findings from this work establish a set of general chemical rules that clarify how siderophores carry out iron acquisition with relevance to nearly all types of bacteria. The interdisciplinary training program enabled by this award allows graduate and undergraduate students in chemistry to gain broad expertise in a variety of modern research techniques relevant to professional careers in science, technology, academics, and industry. A community outreach program is integrated into this project to distribute scientific knowledge to St. Louis area K-12 students and teachers using an interactive metal chelation learning activity that is appropriate for all ages.
Bacteria obtain iron directly from their environment. A variety of strategies evolved by which bacteria carry out this iron acquisition. One such successful strategy is the production of siderophores with high affinity for iron. Chemical and biochemical methods are used to synthesize siderophores and analogs to probe the molecular mechanisms of metal chelation and transport in bacteria. Protein receptor binding studies, bacterial growth experiments, and determination of metal binding affinities establish important siderophore structure-function relationships. Siderophore competition experiments probe for synergy and antagonism of metal acquisition in complex cellular environments. Information from this study guides the discovery of new metal chelation probes that can be used to study metal trafficking in cells, image cellular processes, and target the intracellular delivery of molecular cargo to bacteria. A comprehensive program of education and outreach extends the concepts of metal chelation from the laboratory to the classroom and the community. For example, a hands-on learning activity that demonstrates the chemical basis for iron acquisition can be adapted for students from grades K-12.
