Date: September 12, 2023
Venue: Pulmonary Conference Room (M449) & Zoom
Speaker: Dr. Boone M. Prentice
Affiliation: Department of Chemistry, University of Florida
Title: Spatial metabolomics during infection enabled by imaging mass spectrometry
Abstract: Clostridioides difficile infection (CDI) is one of the most common pathogens affecting the gastrointestinal tract, and has recently been classified as an urgent public health threat worldwide. Interactions between invading pathogens and our gut microbiome are thought to be important during infection, but there are few examples illustrating how these interactions can influence the severity of the invading pathogen. These interactions can also be difficult to study with high molecular specificity, as standard histological techniques used to study infected tissues rely on antibody-based staining workflows, which are unable to differentiate similar target compounds and require a priori knowledge of the targeted molecule of interest. This severely limits the utility of these techniques in the discovery of novel metabolites and limits our ability to discover novel mechanisms of host-microbe interactions and new correlates of disease. To circumvent these limitations, our lab develops imaging mass spectrometry technologies to enable the label-free spatial mapping of metabolites, lipids, glycans, and proteins in thin tissue sections. We have used imaging mass spectrometry to reveal that a group of antibiotic-resistant bacteria in the gut, the enterococci, enhance the growth and severity of CDI. Enterococci are found to act as an energy source of amino acid nutrients, resulting in increased C. difficile growth. Specifically, E. faecalis uptakes arginine through the cell’s ArcD antiporter and concomitantly exports high levels of ornithine during arginine metabolism, which can be used by C. difficile as an energy resource to promote growth and virulence. This evidence of microbial interactions between these two pathogens is remarkable and is demonstrated in multiple mouse models of infection. Overall, imaging mass spectrometry represents a powerful tool for studying the molecular pathology of infection and disease.