CAREER: Elucidating the Roles of Extracellular Metal Ions in Gut Microbiota Interactions

University Of Houston, Houston TX

Investigators

Abstract

With the support of the Chemistry of Life Processes program in the Division of Chemistry, Melissa Zastrow of the University of Houston is studying how metal ions affect cell-cell and cell-host interactions in the gut microbiota. Metal ions such as calcium, iron, and zinc play critical regulatory, catalytic, and structural roles in biology. In gut microbiota, changes to the availability of these essential elements are linked to changes in the colonization of different bacterial species along with infection and disease, but the underlying molecular mechanisms are unclear. The proposed research investigates how metals affect interactions between bacteria and host proteins. Uncovering molecular mechanisms for how metals affect the gut microbiota can lead to novel therapeutics and provide guidance for more effective use of current medical treatments. These studies will be integrated with the development of an interactive bioinorganic training project, the “Inorganic Chemistry at Biological Interfaces” (ICBI) workshop, which is centered on investigating the roles of metal ions at biological interfaces and tailored to undergraduate and graduate students. Participating students will have the opportunity to engage in interdisciplinary research while furthering their growth as scientists. This research project centers on elucidating the fundamental mechanisms through which metals affect cell-cell and cell-host interactions in the gut microbiota. Hundreds of microbial species co-exist in the gastrointestinal tract and can interact via cell-cell or cell-host interactions. Changes in metals could enhance or disrupt these interactions by binding to bacterial cell surfaces, including surface proteins, or host proteins such as mucins. The proposed work will use bacteria from the Lactobacillaceae family and a combination of biochemical and analytical methods to establish mechanisms through which metals affect 1) bacterial cell-cell interactions and 2) cell-host interactions between bacteria and host mucin proteins. To test the effects of metals on cell-cell interactions, biochemical and microscopic characterization will be used to measure biofilm formation in single and multi-species systems. Similar techniques will be used to probe cell-mucin interactions in single and multi-species systems. Site-directed mutagenesis will be used to study the role of surface protein metal-binding sites in mediating both cell-cell and cell-host interactions. Collectively, these studies will test the hypothesis that metals can mediate bacterial interactions in gut microbiota by binding to specific cell surface macromolecules and host proteins. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.