Summary of Study ST002903
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
This study contains a large results data set and is not available in the mwTab file. It is only available for download via FTP as data file(s) here.
| Study ID | ST002903 |
| Study Title | Identification and targeting of microbial putrescine acetylation in bloodstream infections |
| Study Type | comparison of septic shock versus control plasma |
| Study Summary | To identify bacterial metabolites elevated in human plasma during infection, we performed metabolomics on an existing cohort of patient plasma samples from 21 septic shock patients admitted to the intensive care unit (ICU) with culture positive gram-negative BSIs (Escherichia coli, Klebsiella spp., Pseudomonas spp.) who had banked blood samples drawn contemporaneously or near-contemporaneously with their positive blood cultures as well from 22 controls admitted to the ICU for other reasons. |
| Institute | Broad Institute of MIT and Harvard |
| Department | Metabolomics Platform |
| Last Name | Clish |
| First Name | Clary |
| Address | 415 Main Street, Cambridge, MA, 02142, USA |
| clary@broadinstitute.org | |
| Phone | 617-714-7654 |
| Submit Date | 2023-10-02 |
| Num Groups | 2 |
| Total Subjects | 43 |
| Num Males | 19 |
| Num Females | 24 |
| Raw Data Available | Yes |
| Raw Data File Type(s) | raw(Thermo) |
| Analysis Type Detail | LC-MS |
| Release Date | 2023-10-16 |
| Release Version | 1 |
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Project:
| 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 |
