Summary of project PR001807
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 PR001807. The data can be accessed directly via it's Project DOI: 10.21228/M84Q6N This work is supported by NIH grant, U2C- DK119886.
See: https://www.metabolomicsworkbench.org/about/howtocite.php
| Project ID: | PR001807 |
| Project DOI: | doi: 10.21228/M84Q6N |
| Project Title: | A metabolomics pipeline highlights microbial metabolism in bloodstream infections |
| Project Summary: | The growth of antimicrobial resistance (AMR) highlights an urgent need to identify bacterial pathogenic functions that may be targets for clinical intervention. Although severe infections profoundly alter host metabolism, prior studies have largely ignored microbial metabolism in this context. Here we describe an iterative, comparative metabolomics pipeline to uncover microbial metabolic features in the complex setting of a host and apply it to investigate gram-negative bloodstream infection (BSI) in patients. The data from each stage of this analysis pipeline are included here. We find elevated levels of bacterially-derived acetylated polyamines during BSI and discover the enzyme responsible for their production (SpeG). Blocking SpeG activity reduces bacterial proliferation and slows pathogenesis. Reduction of SpeG activity also enhances bacterial membrane permeability and increases intracellular antibiotic accumulation, allowing us to overcome AMR in culture and in vivo. This study highlights how tools to study pathogen metabolism in the natural context of infection can reveal and prioritize new therapeutic strategies for addressing challenging infections. |
| Institute: | Broad Institute of MIT and Harvard |
| Department: | Metabolomics Platform |
| Last Name: | Clish |
| First Name: | Clary |
| Address: | 415 Main Street, Cambridge, MA, 02142, USA |
| Email: | clary@broadinstitute.org |
| Phone: | 617-714-7654 |
| Publications: | submitted |
| Contributors: | Courtney Beaulieu, Amy Deik, Kerry Pierce, Clary B. Clish, Jared R. Mayers, Jack Varon, Ruixuan R. Zhao, Martin Daniel-Ivad, , Amrisha Bholse, Nathanial R. Glasser, Franziska M. Lichtenauer, Julie Ng, Mayra Pinilla Vera, Curtis Huttenhower, Mark A. Perrella, Sihai D. Zhao, Rebecca M. Baron, Emily P. Balskus |
Summary of all studies in project PR001807
| Study ID | Study Title | Species | Institute | Analysis(* : Contains Untargted data) | Release Date | Version | Samples | Download(* : Contains raw data) |
|---|---|---|---|---|---|---|---|---|
| ST002903 | Identification and targeting of microbial putrescine acetylation in bloodstream infections | Homo sapiens | Broad Institute of MIT and Harvard | MS | 2023-10-16 | 1 | 43 | Uploaded data (12.8G)* |
| ST003186 | Untargeted plasma metabolomics on mouse bloodstream infection model with cecal slurry | Mus musculus | Harvard University | MS* | 2024-05-06 | 1 | 19 | Uploaded data (20.1G)* |
| ST003187 | Untargeted plasma metabolomics on bacterial culture supernatants | Escherichia coli | Harvard University | MS* | 2024-05-17 | 1 | 7 | Uploaded data (9G)* |
