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.

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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 IDST002903
Study TitleIdentification and targeting of microbial putrescine acetylation in bloodstream infections
Study Typecomparison of septic shock versus control plasma
Study SummaryTo 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
DepartmentMetabolomics Platform
Last NameClish
First NameClary
Address415 Main Street, Cambridge, MA, 02142, USA
Emailclary@broadinstitute.org
Phone617-714-7654
Submit Date2023-10-02
Num Groups2
Total Subjects43
Num Males19
Num Females24
Raw Data AvailableYes
Raw Data File Type(s)raw(Thermo)
Analysis Type DetailLC-MS
Release Date2023-10-16
Release Version1
Clary Clish Clary Clish
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:Identification and targeting of microbial putrescine acetylation in bloodstream infections
Project Summary:The growth of antimicrobial resistance (AMR) has highlighted an urgent need to identify bacterial pathogenic functions that may be targets for clinical intervention. Although severe bacterial infections profoundly alter host metabolism, prior studies have largely ignored alterations in microbial metabolism in this context. Performing metabolomics on patient plasma samples, we identify elevated levels of bacterially derived N-acetylputrescine during gram-negative bloodstream infections (BSI), with higher levels associated with worse clinical outcomes.
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:SU003016
Subject Type:Human
Subject Species:Homo sapiens
Taxonomy ID:9606
Age Or Age Range:22-93
Gender:Male and female

Factors:

Subject type: Human; Subject species: Homo sapiens (Factor headings shown in green)

mb_sample_id local_sample_id Group
SA315764694Control
SA315765698Control
SA315766700Control
SA315767658Control
SA315768600Control
SA315769597Control
SA315770598Control
SA315771701Control
SA315772650Control
SA315773704Control
SA315774719Control
SA315775720Control
SA315776721Control
SA315777718Control
SA315778712Control
SA315779705Control
SA315780710Control
SA315781596Control
SA315782594Control
SA315783561Control
SA315784392Control
SA315785419Control
SA315786399Septic Shock
SA315787405Septic Shock
SA315788716Septic Shock
SA315789372Septic Shock
SA315790289Septic Shock
SA315791328Septic Shock
SA315792348Septic Shock
SA315793422Septic Shock
SA315794383Septic Shock
SA315795443Septic Shock
SA315796539Septic Shock
SA315797541Septic Shock
SA315798565Septic Shock
SA315799287Septic Shock
SA315800602Septic Shock
SA315801633Septic Shock
SA315802575Septic Shock
SA315803464Septic Shock
SA315804473Septic Shock
SA315805488Septic Shock
SA315806435Septic Shock
Showing results 1 to 43 of 43

Collection:

Collection ID:CO003009
Collection Summary:Patient samples were selected from the pre-existing Registry of Critical Illness (RoCI) cohort, housed at Brigham and Women’s Hospital (BWH) in Boston, MA, USA. RoCI is approved by the Partners Human Research Committee. Informed consent was obtained for blood collection. Curation of the database identified 21 patients with positive blood cultures growing either Escherichia coli, Klebsiella pneumoniae, or Pseudomonas aeruginosa with contemporaneous or near contemporaneous plasma samples banked and available for metabolomic analysis. Twenty-two controls admitted to the intensive care unit for reasons other than septic shock were identified for use as controls.
Sample Type:Blood (plasma)
Storage Conditions:-80℃

Treatment:

Treatment ID:TR003025
Treatment Summary:No treatment was used in the study

Sample Preparation:

Sampleprep ID:SP003022
Sampleprep Summary:Plasma samples were thawed on ice and aliquoted to prepare extracts for three different LC-MS methods: HILIC-pos: 10 µL of plasma sample was extracted using 90 µL of acetonitrile/methanol/formic acid (74.9:24.9:0.2 v/v/v) containing stable isotope-labeled internal standards (valine-d8, Sigma-Aldrich; St. Louis, MO; and phenylalanine-d8, Cambridge Isotope Laboratories; Andover, MA). The samples were centrifuged (10 min, 9,000 x g, 4°C), and the supernatants were transferred to autosampler vials containing deactivated glass inserts. HILIC-neg: 30 µL of each plasma sample was extracted using 120 µL of 80% methanol containing inosine-15N4, thymine-d4 and glycocholate-d4 internal standards (Cambridge Isotope Laboratories; Andover, MA). The samples were centrifuged (10 min, 9,000 x g, 4°C), and the supernatants were transferred to autosampler vials containing deactivated glass inserts. C8-pos: 10 µL of plasma sample was extracted using 190 µL of isopropanol containing 1,2-didodecanoyl-sn-glycero-3-phosphocholine (Avanti Polar Lipids; Alabaster, AL). The samples were centrifuged (10 min, 9,000 x g, ambient temperature), and the supernatants were transferred to autosampler vials containing deactivated glass inserts.

Combined analysis:

Analysis ID AN004762 AN004763 AN004764
Analysis type MS MS MS
Chromatography type HILIC HILIC Reversed phase
Chromatography system Shimadzu Nexera X2 Shimadzu Nexera X2 Shimadzu Nexera X2
Column Waters Atlantis HILIC (150 x 2.1mm,3um,100Å) Phenomenex Luna NH2 (150 x 2 mm,5um,100Å) Waters ACQUITY UPLC BEH C8 (2.1 mm X 100 mm,1.7 µm,130Å)
MS Type ESI ESI ESI
MS instrument type Orbitrap Orbitrap Orbitrap
MS instrument name Thermo Q Exactive Orbitrap Thermo Q Exactive Plus Orbitrap Thermo Exactive Plus Orbitrap
Ion Mode POSITIVE NEGATIVE POSITIVE
Units integrated peak area integrated peak area integrated peak area

Chromatography:

Chromatography ID:CH003594
Chromatography Summary:HILIC-pos: Hydrophilic interaction liquid chromatography (HILIC) analysis of water soluble metabolites in the positive ionization mode
Instrument Name:Shimadzu Nexera X2
Column Name:Waters Atlantis HILIC (150 x 2.1mm,3um,100Å)
Column Temperature:30
Flow Gradient:0-0.5 min, isocratic 95% B; 0.5-10.5 min, gradient to 40% B; 10.5-15 min, isocratic 40% B; 15-17 min, gradient to 95% B
Flow Rate:250 uL/min
Solvent A:100% water; 0.1% formic acid; 10 mM ammonium formate
Solvent B:100% acetonitrile; 0.1% formic acid
Chromatography Type:HILIC
  
Chromatography ID:CH003595
Chromatography Summary:HILIC-neg: Hydrophilic interaction liquid chromatography (HILIC) analysis of water soluble metabolites in the negative ionization mode
Instrument Name:Shimadzu Nexera X2
Column Name:Phenomenex Luna NH2 (150 x 2 mm,5um,100Å)
Column Temperature:30
Flow Gradient:0-10 min, gradient from 90% B to 0% B; 10-12 min, isocratic 0% B; 12-14 min, gradient from 0% B to 90% B
Flow Rate:400 uL/min
Solvent A:100% water; 20 mM ammonium acetate; 20 mM ammonium hydroxide
Solvent B:75% methanol/25% acetonitrile; 10 mM ammonium hydroxide
Chromatography Type:HILIC
  
Chromatography ID:CH003596
Chromatography Summary:C8-pos: Reversed-phase C8 chromatography analysis of polar and nonpolar lipids in the positive ionization mode
Instrument Name:Shimadzu Nexera X2
Column Name:Waters ACQUITY UPLC BEH C8 (2.1 mm X 100 mm,1.7 µm,130Å)
Column Temperature:40
Flow Gradient:0-1 min, isocratic 20% B; 1-3 min, gradient to 80% B; 3-10 min, gradient to 100% B; 10-13 min, isocratic 100% B; 13-14 min, gradient to 20% B
Flow Rate:450 uL/min
Solvent A:95% water/5% methanol; 0.1% formic acid; 10 mM ammonium acetate
Solvent B:100% methanol; 0.1% formic acid
Chromatography Type:Reversed phase

MS:

MS ID:MS004508
Analysis ID:AN004762
Instrument Name:Thermo Q Exactive Orbitrap
Instrument Type:Orbitrap
MS Type:ESI
MS Comments:MS analyses were carried out using electrospray ionization in the positive ion mode using full scan analysis over 70-800 m/z at 70,000 resolution and 3 Hz data acquisition rate. Other MS settings were: sheath gas 40, sweep gas 2, spray voltage 3.5 kV, capillary temperature 350°C, S-lens RF 40, heater temperature 300°C, microscans 1, automatic gain control target 1e6, and maximum ion time 250 ms. Raw data were processed using TraceFinder 3.3 software (Thermo Fisher Scientific; Waltham, MA) and Progenesis QI (Nonlinear Dynamics; Newcastle upon Tyne, UK). Metabolite identities were confirmed using authentic reference standards.
Ion Mode:POSITIVE
  
MS ID:MS004509
Analysis ID:AN004763
Instrument Name:Thermo Q Exactive Plus Orbitrap
Instrument Type:Orbitrap
MS Type:ESI
MS Comments:MS analyses were carried out using electrospray ionization in the negative ion mode using full scan analysis over m/z 70-750 at 70,000 resolution and 3 Hz data acquisition rate. Additional MS settings were: ion spray voltage, -3.0 kV; capillary temperature, 350°C; probe heater temperature, 325 °C; sheath gas, 55; auxiliary gas, 10; and S-lens RF level 50. Raw data were processed using TraceFinder 3.3 software (Thermo Fisher Scientific; Waltham, MA) and Progenesis QI (Nonlinear Dynamics; Newcastle upon Tyne, UK). Metabolite identities were confirmed using authentic reference standards.
Ion Mode:NEGATIVE
  
MS ID:MS004510
Analysis ID:AN004764
Instrument Name:Thermo Exactive Plus Orbitrap
Instrument Type:Orbitrap
MS Type:ESI
MS Comments:MS analyses were carried out using electrospray ionization in the positive ion mode using full scan analysis over 200–1100 m/z at 70,000 resolution and 3 Hz data acquisition rate. Other MS settings were: sheath gas 50, in source CID 5 eV, sweep gas 5, spray voltage 3 kV, capillary temperature 300°C, S-lens RF 60, heater temperature 300°C, microscans 1, automatic gain control target 1e6, and maximum ion time 100 ms. Representative standards from each lipid class were used to identify lipids based on RT and m/z patterns, and characteristic product ion spectra. Lipid identities were denoted by total acyl carbon number and total number of double bond number.
Ion Mode:POSITIVE
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