Summary of Study ST000453
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 PR000350. The data can be accessed directly via it's Project DOI: 10.21228/M8T30C This work is supported by NIH grant, U2C- DK119886.
See: https://www.metabolomicsworkbench.org/about/howtocite.php
Study ID | ST000453 |
Study Title | Metabolic Adaptation of Staphylococcus aureus to Host Immunity |
Study Type | Metabolomics Analysis of Methicillin-Resistant Staphylococcus aureus (MRSA) to host immunity. |
Study Summary | This project is intended to study the metabolic adaptation of Methicillin-Resistant Staphylococcus aureus (MRSA) to host immunity. Because of the nature of the samples RTI RCMRC worked with Dr. Anthony R. Richardson so that the samples would be extracted at the University of North Carolina at Chapel Hill under the condition that were optimized by RTI RCMRC for broad spectrum metabolomics analysis. |
Institute | University of North Carolina |
Department | RCMRC |
Laboratory | Sumner Lab |
Last Name | Sumner |
First Name | Susan |
Address | Eastern Regional Comprehensive Metabolomics Resource Core, UNC Nutrition Research Institute, 500 Laureate Way, Kannapolis, NC, 28081 |
susan_sumner @unc.edu | |
Phone | 704-250-5066 |
Submit Date | 2017-09-10 |
Num Groups | 29 |
Total Subjects | 29 |
Raw Data Available | Yes |
Raw Data File Type(s) | wiff |
Analysis Type Detail | LC-MS |
Release Date | 2017-10-03 |
Release Version | 1 |
Select appropriate tab below to view additional metadata details:
Project:
Project ID: | PR000350 |
Project DOI: | doi: 10.21228/M8T30C |
Project Title: | Metabolic Adaptation of Staphylococcus aureus to Host Immunity |
Project Summary: | Staphylococcus aureus infections are difficult to treat given the drug-resistant nature of this bacterium. Methicillin-Resistant Staphylococcus aureus (MRSA) is considered the single most deadly bacterial infection in the United States. The bacterium resists nearly every aspect of innate immunity, including the cytotoxic effects of nitric oxide (NO?) which is an innate immune effector produced by phagocytes in response to infection. NO? interferes with various metabolic pathways in pathogens by reacting with redox centers of multiple enzymes. We have demonstrated that S. aureus NO?-resistance is essential for full virulence. We have also shown that S. aureus NO-resistance is predicated on the abundance of glucose, which may explain exacerbated S. aureus disease outcomes associated with diabetic patients having poorly controlled blood sugar. Here we propose to employ metabolomics to probe the nature of the S. aureus NO-resistant metabolic state. We will thereby bridge a fundamental gap in our knowledge of S. aureus pathogenesis by defining metabolic pathways essential to cause disease in immunocompetent hosts. These key metabolic pathways represent important therapeutic targets for future research. Define the requirement for glycolytic carbon/energy sources for the S. aureus NO-RMS: While S. aureus can thrive on a variety of gluconeogenic carbon sources (e.g. amino acids, glycerol, lactate etc.), none of these are capable of supporting NO?-resistance. We will compare changes in intracellular metabolites in cells growing on gluconeogenic carbon sources following NO?-exposure to elucidate what features of gluconeogenesis are incompatible with NO?-resistance. The absolute requirement for glycolytic carbon sources for NO-resistance is interesting given the disproportionately poor disease outcomes of MRSA infections in diabetic patients with elevated blood glucose. |
Institute: | University of North Carolina at Chapel Hill |
Department: | Department of Microbiology and Immnunology, UNC-CH |
Last Name: | Richardson |
First Name: | Anthony |
Address: | 125 Mason Farm Rd, Marsico Hall 6209, Chapel Hill, NC 27599 |
Email: | anthony_richardson@med.unc.edu |
Phone: | 919-843-3654 |
Subject:
Subject ID: | SU000474 |
Subject Type: | Bacterial Cells |
Subject Species: | Staphylococcus aureus |
Taxonomy ID: | 1280 |
Species Group: | Bacteria |
Factors:
Subject type: Bacterial Cells; Subject species: Staphylococcus aureus (Factor headings shown in green)
mb_sample_id | local_sample_id | Cell | Additive 1 | Additive 2 | Environment | NO status | Time |
---|---|---|---|---|---|---|---|
SA022900 | Total_Pool_02 | - | - | - | - | - | - |
SA022901 | Total_Pool_01 | - | - | - | - | - | - |
SA022902 | Total_Pool_03 | - | - | - | - | - | - |
SA022903 | Total_Pool_04 | - | - | - | - | - | - |
SA022904 | Total_Pool_05 | - | - | - | - | - | - |
SA022908 | CE_mut_G_NO_1_5_27_C | mutant | Glucose | none | undefined | NO | 1.5 h |
SA022909 | CE_mut_G_NO_1_5_27_A | mutant | Glucose | none | undefined | NO | 1.5 h |
SA022910 | CE_mut_G_NO_1_5_27_B | mutant | Glucose | none | undefined | NO | 1.5 h |
SA022905 | CE_mut_G_NO_1_26_B | mutant | Glucose | none | undefined | NO | 1 h |
SA022906 | CE_mut_G_NO_1_26_C | mutant | Glucose | none | undefined | NO | 1 h |
SA022907 | CE_mut_G_NO_1_26_A | mutant | Glucose | none | undefined | NO | 1 h |
SA022911 | CE_mut_G_NO_3_28_C | mutant | Glucose | none | undefined | NO | 5 h |
SA022912 | CE_mut_G_NO_3_28_B | mutant | Glucose | none | undefined | NO | 5 h |
SA022913 | CE_mut_G_NO_3_28_A | mutant | Glucose | none | undefined | NO | 5 h |
SA022914 | CE_mut_G_NO_4_29_A | mutant | Glucose | none | undefined | NO | 6 h |
SA022915 | CE_mut_G_NO_4_29_B | mutant | Glucose | none | undefined | NO | 6 h |
SA022916 | CE_mut_G_NO_4_29_C | mutant | Glucose | none | undefined | NO | 6 h |
SA022917 | CE_AA_A_3_A | normal | AA | none | Aerobic | not specified | not specified |
SA022918 | CE_AA_A_3_C | normal | AA | none | Aerobic | not specified | not specified |
SA022919 | CE_AA_A_3_B | normal | AA | none | Aerobic | not specified | not specified |
SA022920 | CE_AA_NO_0_25_18_C | normal | AA | none | undefined | NO | 0.25 h |
SA022921 | CE_AA_NO_0_25_18_A | normal | AA | none | undefined | NO | 0.25 h |
SA022922 | CE_AA_NO_0_25_18_B | normal | AA | none | undefined | NO | 0.25 h |
SA022923 | CE_AA_NO_0_5_19_C | normal | AA | none | undefined | NO | 0.5 h |
SA022924 | CE_AA_NO_0_5_19_A | normal | AA | none | undefined | NO | 0.5 h |
SA022925 | CE_AA_NO_0_5_19_B | normal | AA | none | undefined | NO | 0.5 h |
SA022926 | CE_AA_NO_1_5_21_A | normal | AA | none | undefined | NO | 1.5 h |
SA022927 | CE_AA_NO_1_5_21_C | normal | AA | none | undefined | NO | 1.5 h |
SA022928 | CE_AA_NO_1_5_21_B | normal | AA | none | undefined | NO | 1.5 h |
SA022932 | CE_AA_NO_2_5_23_A | normal | AA | none | undefined | NO | 2.5 h |
SA022933 | CE_AA_NO_2_5_23_B | normal | AA | none | undefined | NO | 2.5 h |
SA022934 | CE_AA_NO_2_5_23_C | normal | AA | none | undefined | NO | 2.5 h |
SA022929 | CE_AA_NO_2_17_B | normal | AA | none | undefined | NO | 2 h |
SA022930 | CE_AA_NO_2_17_A | normal | AA | none | undefined | NO | 2 h |
SA022931 | CE_AA_NO_2_17_C | normal | AA | none | undefined | NO | 2 h |
SA022935 | CE_AA_NO_3_24_A | normal | AA | none | undefined | NO | 3 h |
SA022936 | CE_AA_NO_3_24_C | normal | AA | none | undefined | NO | 3 h |
SA022937 | CE_AA_NO_1_20_B | normal | AA | none | undefined | NO | 3 h |
SA022938 | CE_AA_NO_3_24_B | normal | AA | none | undefined | NO | 3 h |
SA022939 | CE_AA_NO_1_20_C | normal | AA | none | undefined | NO | 3 h |
SA022940 | CE_AA_NO_1_20_A | normal | AA | none | undefined | NO | 3 h |
SA022941 | CE_AA_NO_4_25_A | normal | AA | none | undefined | NO | 4 h |
SA022942 | CE_AA_NO_4_25_C | normal | AA | none | undefined | NO | 4 h |
SA022943 | CE_AA_NO_4_25_B | normal | AA | none | undefined | NO | 4 h |
SA022944 | CE_AA_NO_2_22_A | normal | AA | none | undefined | NO | 4 h |
SA022945 | CE_AA_NO_2_22_B | normal | AA | none | undefined | NO | 4 h |
SA022946 | CE_AA_NO_2_22_C | normal | AA | none | undefined | NO | 4 h |
SA022947 | CE_AA_P_A_4_A | normal | AA | pyruvate | Aerobic | not specified | not specified |
SA022948 | CE_AA_P_A_4_C | normal | AA | pyruvate | Aerobic | not specified | not specified |
SA022949 | CE_AA_P_A_4_B | normal | AA | pyruvate | Aerobic | not specified | not specified |
SA022950 | CE_G_A_1_A | normal | Glucose | none | Aerobic | not specified | not specified |
SA022951 | CE_G_A_1_C | normal | Glucose | none | Aerobic | not specified | not specified |
SA022952 | CE_G_A_1_B | normal | Glucose | none | Aerobic | not specified | not specified |
SA022953 | CE_G_AN_NO2_8_A | normal | Glucose | none | Anaerobic | NO2 | not specified |
SA022954 | CE_G_AN_NO2_8_B | normal | Glucose | none | Anaerobic | NO2 | not specified |
SA022955 | CE_G_AN_NO2_8_C | normal | Glucose | none | Anaerobic | NO2 | not specified |
SA022956 | CE_G_AN_NO3_7_C | normal | Glucose | none | Anaerobic | NO3 | not specified |
SA022957 | CE_G_AN_NO3_7_B | normal | Glucose | none | Anaerobic | NO3 | not specified |
SA022958 | CE_G_AN_NO3_7_A | normal | Glucose | none | Anaerobic | NO3 | not specified |
SA022959 | CE_G_AN_5_C | normal | Glucose | none | Anaerobic | not specified | not specified |
SA022960 | CE_G_AN_5_A | normal | Glucose | none | Anaerobic | not specified | not specified |
SA022961 | CE_G_AN_5_B | normal | Glucose | none | Anaerobic | not specified | not specified |
SA022962 | CE_G_HY_6_C | normal | Glucose | none | Hypoxic | not specified | not specified |
SA022963 | CE_G_HY_6_B | normal | Glucose | none | Hypoxic | not specified | not specified |
SA022964 | CE_G_HY_6_A | normal | Glucose | none | Hypoxic | not specified | not specified |
SA022965 | CE_G_NO_0_25_9_A | normal | Glucose | none | undefined | NO | 0.25 h |
SA022966 | CE_G_NO_0_25_9_C | normal | Glucose | none | undefined | NO | 0.25 h |
SA022967 | CE_G_NO_0_25_9_B | normal | Glucose | none | undefined | NO | 0.25 h |
SA022968 | CE_G_NO_0_5_10_A | normal | Glucose | none | undefined | NO | 0.5 h |
SA022969 | CE_G_NO_0_5_10_B | normal | Glucose | none | undefined | NO | 0.5 h |
SA022970 | CE_G_NO_0_5_10_C | normal | Glucose | none | undefined | NO | 0.5 h |
SA022974 | CE_G_NO_1_5_12_C | normal | Glucose | none | undefined | NO | 1.5 h |
SA022975 | CE_G_NO_1_5_12_A | normal | Glucose | none | undefined | NO | 1.5 h |
SA022976 | CE_G_NO_1_5_12_B | normal | Glucose | none | undefined | NO | 1.5 h |
SA022971 | CE_G_NO_1_11_A | normal | Glucose | none | undefined | NO | 1 h |
SA022972 | CE_G_NO_1_11_C | normal | Glucose | none | undefined | NO | 1 h |
SA022973 | CE_G_NO_1_11_B | normal | Glucose | none | undefined | NO | 1 h |
SA022980 | CE_G_NO_2_5_14_C | normal | Glucose | none | undefined | NO | 2.5 h |
SA022981 | CE_G_NO_2_5_14_B | normal | Glucose | none | undefined | NO | 2.5 h |
SA022982 | CE_G_NO_2_5_14_A | normal | Glucose | none | undefined | NO | 2.5 h |
SA022977 | CE_G_NO_2_13_A | normal | Glucose | none | undefined | NO | 2 h |
SA022978 | CE_G_NO_2_13_B | normal | Glucose | none | undefined | NO | 2 h |
SA022979 | CE_G_NO_2_13_C | normal | Glucose | none | undefined | NO | 2 h |
SA022983 | CE_G_NO_3_15_B | normal | Glucose | none | undefined | NO | 3 h |
SA022984 | CE_G_NO_3_15_C | normal | Glucose | none | undefined | NO | 3 h |
SA022985 | CE_G_NO_3_15_A | normal | Glucose | none | undefined | NO | 3 h |
SA022986 | CE_G_NO_5_16_B | normal | Glucose | none | undefined | NO | 5 h |
SA022987 | CE_G_NO_5_16_C | normal | Glucose | none | undefined | NO | 5 h |
SA022988 | CE_G_NO_5_16_A | normal | Glucose | none | undefined | NO | 5 h |
SA022989 | CE_G_P_A_2_C | normal | Glucose | pyruvate | Aerobic | not specified | not specified |
SA022990 | CE_G_P_A_2_A | normal | Glucose | pyruvate | Aerobic | not specified | not specified |
SA022991 | CE_G_P_A_2_B | normal | Glucose | pyruvate | Aerobic | not specified | not specified |
Showing results 1 to 92 of 92 |
Collection:
Collection ID: | CO000468 |
Collection Summary: | Cultures of S. aureus strain COL |
Sample Type: | Bacterial cells |
Treatment:
Treatment ID: | TR000488 |
Treatment Summary: | Glucose NO 5 h AA NO 3 h Glucose Anaer Glucose NO 2 h Glucose Hypoxic Glucose Aerobic a.a. + Pyr Aer Glucose NO .25 h Glucose Anaerobic NO3 AA NO 1.5 h Glucose NO 3 h AA NO 2 h mut Gluc NO 1.5 h Glucose Anaerobic NO2 mut Gluc NO 3 h AA NO .5 h mut Gluc NO 4 h AA NO .25 h Glucose NO 1 h mut Gluc NO 1 h AA NO 4 h AA NO 2.5 h Glucose NO 2.5 h AA NO 1 h Glucose NO 1.5 h AA NO 2 h Glucose NO .5 h a.a. Aer Glucose + Pyruvate Aerobic |
Sample Preparation:
Sampleprep ID: | SP000481 |
Sampleprep Summary: | Methylillin-resistant S. aureus (MRSA) bacterial culture extracts re-suspended in water were provided to RTI RCMRC for analysis. These extracts were stored at -80 °C upon arrival. For processing, samples were dried overnight on a lyophilizer. The residue was then reconstituted with 150 µL of an ice-cold solution of reconstitution buffer (0.005 mg/mL Tryptophan-d5 in 95:5 Water:Methanol, v/v) and mixed on a multiple tube vortexer for 2 min at 5,000 rpm. Then, the samples were centrifuged at room temperature for 4 min at 16,000 rcf, and 100 µL of the supernatants were transferred to autosampler vials for data acquisition. Whole study pooled QC samples were created by combining 40 µL aliquot from each of the reconstituted samples into a 2 mL LoBind eppendorf tube. The QC pooled sample was then vortexed for 15 sec and 100 µL of the total study pooled QC samples were transferred to five pre-labeled autosampler vials. |
Combined analysis:
Analysis ID | AN000709 | AN000710 |
---|---|---|
Analysis type | MS | MS |
Chromatography type | Reversed phase | Reversed phase |
Chromatography system | Waters Acquity | Waters Acquity |
Column | Waters Acquity HSS T3 (100 x 2.1mm,1.8um) | Waters Acquity HSS T3 (100 x 2.1mm,1.8um) |
MS Type | ESI | ESI |
MS instrument type | QTOF | QTOF |
MS instrument name | Waters Synapt-G2-Si | Waters Synapt-G2-Si |
Ion Mode | POSITIVE | NEGATIVE |
Units | counts | counts |
Chromatography:
Chromatography ID: | CH000513 |
Instrument Name: | Waters Acquity |
Column Name: | Waters Acquity HSS T3 (100 x 2.1mm,1.8um) |
Column Pressure: | 6,000-10,000 psi |
Column Temperature: | 50 °C |
Flow Rate: | 0.4 mL/min |
Injection Temperature: | 8 °C |
Solvent A: | 100% water; 0.1% formic acid |
Solvent B: | 100% methanol; 0.1% formic acid |
Analytical Time: | 22 min |
Randomization Order: | Yes |
Chromatography Type: | Reversed phase |
MS:
MS ID: | MS000631 |
Analysis ID: | AN000709 |
Instrument Name: | Waters Synapt-G2-Si |
Instrument Type: | QTOF |
MS Type: | ESI |
Ion Mode: | POSITIVE |
MS ID: | MS000632 |
Analysis ID: | AN000710 |
Instrument Name: | Waters Synapt-G2-Si |
Instrument Type: | QTOF |
MS Type: | ESI |
Ion Mode: | NEGATIVE |