Summary of Study ST003186
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 | ST003186 |
| Study Title | Untargeted plasma metabolomics on mouse bloodstream infection model with cecal slurry |
| Study Summary | As part of our pipeline to identify microbial metabolites in bloodstream infections, we performed untargeted metabolomics on plasma from male B6 mice that developed bloodstream infections as result of an injection of cecal slurry. More specifically, we harvested plasma 24hrs after IP injection of PBS, heat killed cecal slurry, or live cecal slurry. The comparison of heat killed cecal slurry vs live cecal slurry allows us to tease apart metabolite alterations due to the host response to an infectious insult vs metabolite changes produced by live bacteria. For this analysis, we specifically focused on the metabolites significantly altered in our human cohort (PR001807). Metabolites that were altered in this model were then examined in microbial culture experiments |
| Institute | Harvard University |
| Last Name | Mayers |
| First Name | Jared |
| Address | 12 Oxford St Conant 200S Cambridge, MA 02138 |
| jrmayers@gmail.com | |
| Phone | 4259417747 |
| Submit Date | 2024-04-26 |
| Raw Data Available | Yes |
| Raw Data File Type(s) | mzML |
| Analysis Type Detail | LC-MS |
| Release Date | 2024-05-06 |
| Release Version | 1 |
Select appropriate tab below to view additional metadata details:
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 |
Subject:
| Subject ID: | SU003305 |
| Subject Type: | Mammal |
| Subject Species: | Mus musculus |
| Taxonomy ID: | 10090 |
| Species Group: | Mammals |
Factors:
Subject type: Mammal; Subject species: Mus musculus (Factor headings shown in green)
| mb_sample_id | local_sample_id | Factor | Sample source |
|---|---|---|---|
| SA346811 | 24hr_10 | Control | Plasma |
| SA346812 | 24hr_1 | Control | Plasma |
| SA346813 | 24hr_13 | Control | Plasma |
| SA346814 | 24hr_7 | Control | Plasma |
| SA346815 | 24hr_16 | Control | Plasma |
| SA346816 | 24hr_19 | Control | Plasma |
| SA346817 | 24hr_4 | Control | Plasma |
| SA346818 | 24hr_22 | Control | Plasma |
| SA346819 | 24hr_23 | Heat Killed | Plasma |
| SA346820 | 24hr_14 | Heat Killed | Plasma |
| SA346821 | 24hr_17 | Heat Killed | Plasma |
| SA346822 | 24hr_11 | Heat Killed | Plasma |
| SA346823 | 24hr_2 | Heat Killed | Plasma |
| SA346824 | 24hr_5 | Heat Killed | Plasma |
| SA346825 | 24hr_8 | Heat Killed | Plasma |
| SA346826 | 24hr_24 | Live | Plasma |
| SA346827 | 24hr_3 | Live | Plasma |
| SA346828 | 24hr_12 | Live | Plasma |
| SA346829 | 24hr_6 | Live | Plasma |
| Showing results 1 to 19 of 19 |
Collection:
| Collection ID: | CO003298 |
| Collection Summary: | Plasma samples from terminal bleed via cardiac puncture under anesthesia |
| Sample Type: | Blood (plasma) |
Treatment:
| Treatment ID: | TR003314 |
| Treatment Summary: | IP injection with either PBS, heat killed cecal slurry or live cecal slurry 24hrs prior to blood draw |
Sample Preparation:
| Sampleprep ID: | SP003312 |
| Sampleprep Summary: | 1 part plasma with 9 parts 75:25:0.2 ACN:MetOH:Formic Acid with internal val-d8 and phe-d8 standards; vortexed, centrifuged, supernatant removed and run on LC-MS |
Combined analysis:
| Analysis ID | AN005234 |
|---|---|
| Analysis type | MS |
| Chromatography type | HILIC |
| Chromatography system | Agilent 1260 Infinity HPLC |
| Column | Waters Atlantis HILIC (150 x 2.1mm,3um) |
| MS Type | ESI |
| MS instrument type | QTOF |
| MS instrument name | Agilent 6530 QTOF |
| Ion Mode | POSITIVE |
| Units | ion counts |
Chromatography:
| Chromatography ID: | CH003961 |
| Instrument Name: | Agilent 1260 Infinity HPLC |
| Column Name: | Waters Atlantis HILIC (150 x 2.1mm,3um) |
| Column Temperature: | 30 |
| Flow Gradient: | 0.5 minute at 5% mobile phase B followed by a linear gradient to 40% mobile phase B over 10 minutes and then maintained isocratically for 4.5 minutes before returning to 5% mobile phase B by gradient over 2 minutes |
| Flow Rate: | 250 μL/min |
| Solvent A: | 100% water; 0.1% formic acid |
| Solvent B: | 100% acetonitrile; 0.1% formic acid |
| Chromatography Type: | HILIC |
MS:
| MS ID: | MS004967 |
| Analysis ID: | AN005234 |
| Instrument Name: | Agilent 6530 QTOF |
| Instrument Type: | QTOF |
| MS Type: | ESI |
| MS Comments: | Raw data from the LC–MS were analyzed using Agilent MassHunter Qualitative Analysis 10.0 software. |
| Ion Mode: | POSITIVE |
