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.

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Study IDST003186
Study TitleUntargeted plasma metabolomics on mouse bloodstream infection model with cecal slurry
Study SummaryAs 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 NameMayers
First NameJared
Address12 Oxford St Conant 200S Cambridge, MA 02138
Emailjrmayers@gmail.com
Phone4259417747
Submit Date2024-04-26
Raw Data AvailableYes
Raw Data File Type(s)mzML
Analysis Type DetailLC-MS
Release Date2024-05-06
Release Version1
Jared Mayers Jared Mayers
https://dx.doi.org/10.21228/M84Q6N
ftp://www.metabolomicsworkbench.org/Studies/ application/zip

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

Factors:

Subject type: Mammal; Subject species: Mus musculus (Factor headings shown in green)

mb_sample_id local_sample_id Factor Sample source
SA34681124hr_10Control Plasma
SA34681224hr_1Control Plasma
SA34681324hr_13Control Plasma
SA34681424hr_7Control Plasma
SA34681524hr_16Control Plasma
SA34681624hr_19Control Plasma
SA34681724hr_4Control Plasma
SA34681824hr_22Control Plasma
SA34681924hr_23Heat Killed Plasma
SA34682024hr_14Heat Killed Plasma
SA34682124hr_17Heat Killed Plasma
SA34682224hr_11Heat Killed Plasma
SA34682324hr_2Heat Killed Plasma
SA34682424hr_5Heat Killed Plasma
SA34682524hr_8Heat Killed Plasma
SA34682624hr_24Live Plasma
SA34682724hr_3Live Plasma
SA34682824hr_12Live Plasma
SA34682924hr_6Live 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
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