Summary of project PR001566
This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench, https://www.metabolomicsworkbench.org, where it has been assigned Project ID PR001566. The data can be accessed directly via it's Project DOI: 10.21228/M88M5G This work is supported by NIH grant, U2C- DK119886.
See: https://www.metabolomicsworkbench.org/about/howtocite.php
| Project ID: | PR001566 |
| Project DOI: | doi: 10.21228/M88M5G |
| Project Title: | Elucidating dynamic anaerobe metabolism with HRMAS 13C NMR and genome-scale modeling |
| Project Summary: | Anaerobic microbial metabolism drives critical functions within global ecosystems, host-microbiota interactions, and industrial applications, yet remains ill-defined. Here we advance a versatile approach to elaborate cellular metabolism in obligate anaerobes using the pathogen Clostridioides difficile, an amino acid and carbohydrate-fermenting Clostridia. High-Resolution Magic Angle Spinning (HRMAS) Nuclear Magnetic Resonance (NMR) spectroscopy of C. difficile, grown with fermentable 13C substrates, informed dynamic flux balance analysis (dFBA) of the pathogen’s genome-scale metabolism. Analyses identified dynamic recruitment of oxidative and supporting reductive pathways, with integration of high-flux amino acid and glycolytic metabolism at alanine’s biosynthesis to support efficient energy generation, nitrogen handling, and biomass generation. Model predictions informed an approach leveraging the sensitivity of 13C NMR spectroscopy to simultaneously track cellular carbon and nitrogen flow from [U-13C]glucose and [15N]leucine, confirming the formation of [13C,15N]alanine. Findings identify metabolic strategies used by C. difficile to support its rapid colonization and expansion in gut ecosystems. |
| Institute: | Brigham and Women's Hospital |
| Department: | Pathology |
| Laboratory: | Bry Lab (Massachusetts Host-Microbiome Center, BWH) and Cheng Lab (Massachusetts General Hospital) |
| Last Name: | Pavao |
| First Name: | Aidan |
| Address: | 221 Longwood Ave, EBRC-411, Boston, MA, 02115, USA |
| Email: | apavao2@bwh.harvard.edu |
| Phone: | 617-525-7184 |
| Funding Source: | NIH R01AI153653, R03AI174158, P30DK056338, S10OD023406, R21CA243255, and R01AG070257; BWH Precision Medicine Institute; MGH A. A. Martinos Center for Biomedical Imaging |
| Publications: | https://doi.org/10.1038/s41589-023-01275-9 |
| Contributors: | Aidan Pavao, Brintha Girinathan, Johann Peltier, Pamela Altamirano Silva, Bruno Dupuy, Isabella H. Muti, Craig Malloy, Leo L. Cheng, Lynn Bry |
Summary of all studies in project PR001566
| Study ID | Study Title | Species | Institute | Analysis(* : Contains Untargted data) | Release Date | Version | Samples | Download(* : Contains raw data) |
|---|---|---|---|---|---|---|---|---|
| ST002433 | Elucidating dynamic anaerobe metabolism with HRMAS 13C NMR and genome-scale modeling | Clostridioides difficile | Brigham and Women's Hospital | NMR | 2023-01-20 | 1 | 20 | Uploaded data (1.1G)* |
