Summary of Study ST003973

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 PR002489. The data can be accessed directly via it's Project DOI: 10.21228/M8X267 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 IDST003973
Study TitleTrehalose catalytic shift inherently enhances phenotypic heterogeneity and multidrug resistance in Mycobacterium tuberculosis
Study SummaryDrug-resistance (DR) in bacteria often develops through the repetitive formation of drug-tolerant persister cells, which survive antibiotics without genetic changes. It is unclear whether Mycobacterium tuberculosis (Mtb), the bacterium that causes tuberculosis (TB), undergoes a similar transitioning process. Recent studies highlight changes in trehalose metabolism as crucial for Mtb persister formation and drug resistance. In this study, we observe that mutants lacking trehalose catalytic shift activity exhibited fewer DR mutants due to decreased persisters. This shift enhances Mtb survival during antibiotic treatment by increasing metabolic heterogeneity and drug tolerance, facilitating drug-resistance. Rifampicin (RIF)-resistant bacilli display cross-resistance to other antibiotics linked to higher trehalose catalytic shift, explaining how multidrug resistance (MDR) can follow RIF-resistance. In particular, the HN878 W-Beijing strain exhibits higher trehalose catalytic shift, increasing MDR risk. Both genetic and pharmacological inactivation of this shift reduces persister formation and MDR development, suggesting trehalose catalytic shift as a potential therapeutic target to combat TB resistance.
Institute
University of Southern California
Last NameEoh
First NameHyungjin
Address1501 San Pablo Street, Los Angeles, CA, 90033, USA
Emailheoh@usc.edu
Phone323-442-6048
Submit Date2025-06-09
PublicationsJaejin Lee. et al. Trehalose catalytic shift inherently enhances phenotypic heterogeneity and multidrug resistance in Mycobacterium tuberculosis. Nat. Comm.
Raw Data AvailableYes
Raw Data File Type(s)mzML
Analysis Type DetailLC-MS
Release Date2025-07-03
Release Version1
Hyungjin Eoh Hyungjin Eoh
https://dx.doi.org/10.21228/M8X267
ftp://www.metabolomicsworkbench.org/Studies/ application/zip

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Project:

Project ID:PR002489
Project DOI:doi: 10.21228/M8X267
Project Title:Trehalose catalytic shift inherently enhances phenotypic heterogeneity and multidrug resistance in Mycobacterium tuberculosis
Project Summary:Drug-resistance (DR) in bacteria often develops through the repetitive formation of drug-tolerant persister cells, which survive antibiotics without genetic changes. It is unclear whether Mycobacterium tuberculosis (Mtb), the bacterium that causes tuberculosis (TB), undergoes a similar transitioning process. Recent studies highlight changes in trehalose metabolism as crucial for Mtb persister formation and drug resistance. In this study, we observe that mutants lacking trehalose catalytic shift activity exhibited fewer DR mutants due to decreased persisters. This shift enhances Mtb survival during antibiotic treatment by increasing metabolic heterogeneity and drug tolerance, facilitating drug-resistance. Rifampicin (RIF)-resistant bacilli display cross-resistance to other antibiotics linked to higher trehalose catalytic shift, explaining how multidrug resistance (MDR) can follow RIF-resistance. In particular, the HN878 W-Beijing strain exhibits higher trehalose catalytic shift, increasing MDR risk. Both genetic and pharmacological inactivation of this shift reduces persister formation and MDR development, suggesting trehalose catalytic shift as a potential therapeutic target to combat TB resistance.
Institute:University of Southern California
Last Name:Eoh
First Name:Hyungjin
Address:1501 San Pablo Street, Los Angeles, CA, 90033, USA
Email:heoh@usc.edu
Phone:323-442-6048

Subject:

Subject ID:SU004110
Subject Type:Bacteria
Subject Species:Mycobacterium tuberculosis

Factors:

Subject type: Bacteria; Subject species: Mycobacterium tuberculosis (Factor headings shown in green)

mb_sample_id local_sample_id Sample source treatment
SA453529022020_03extensively drug-resistant strain Control
SA453530P022020_03extensively drug-resistant strain Control
SA453531P022020_27extensively drug-resistant strain Control
SA453532P022020_26extensively drug-resistant strain Control
SA453533P022020_25extensively drug-resistant strain Control
SA453534P022020_21extensively drug-resistant strain Control
SA453535P022020_20extensively drug-resistant strain Control
SA453536P022020_19extensively drug-resistant strain Control
SA453537P022020_15extensively drug-resistant strain Control
SA453538P022020_14extensively drug-resistant strain Control
SA453539P022020_13extensively drug-resistant strain Control
SA453540P022020_09extensively drug-resistant strain Control
SA453541P022020_08extensively drug-resistant strain Control
SA453542P022020_07extensively drug-resistant strain Control
SA453543P022020_02extensively drug-resistant strain Control
SA453544P022020_33extensively drug-resistant strain Control
SA453545P022020_01extensively drug-resistant strain Control
SA453546022020_87extensively drug-resistant strain Control
SA453547022020_86extensively drug-resistant strain Control
SA453548022020_85extensively drug-resistant strain Control
SA453549022020_81extensively drug-resistant strain Control
SA453550022020_80extensively drug-resistant strain Control
SA453551022020_79extensively drug-resistant strain Control
SA453552022020_75extensively drug-resistant strain Control
SA453553022020_74extensively drug-resistant strain Control
SA453554022020_73extensively drug-resistant strain Control
SA453555022020_69extensively drug-resistant strain Control
SA453556022020_68extensively drug-resistant strain Control
SA453557P022020_32extensively drug-resistant strain Control
SA453558P022020_37extensively drug-resistant strain Control
SA453559022020_63extensively drug-resistant strain Control
SA453560P022020_68extensively drug-resistant strain Control
SA453561022020_01extensively drug-resistant strain Control
SA453562022020_02extensively drug-resistant strain Control
SA453563P022020_87extensively drug-resistant strain Control
SA453564P022020_86extensively drug-resistant strain Control
SA453565P022020_85extensively drug-resistant strain Control
SA453566P022020_81extensively drug-resistant strain Control
SA453567P022020_80extensively drug-resistant strain Control
SA453568P022020_79extensively drug-resistant strain Control
SA453569P022020_75extensively drug-resistant strain Control
SA453570P022020_74extensively drug-resistant strain Control
SA453571P022020_73extensively drug-resistant strain Control
SA453572P022020_69extensively drug-resistant strain Control
SA453573P022020_67extensively drug-resistant strain Control
SA453574P022020_38extensively drug-resistant strain Control
SA453575P022020_63extensively drug-resistant strain Control
SA453576P022020_62extensively drug-resistant strain Control
SA453577P022020_61extensively drug-resistant strain Control
SA453578P022020_57extensively drug-resistant strain Control
SA453579P022020_56extensively drug-resistant strain Control
SA453580P022020_55extensively drug-resistant strain Control
SA453581P022020_51extensively drug-resistant strain Control
SA453582P022020_50extensively drug-resistant strain Control
SA453583P022020_49extensively drug-resistant strain Control
SA453584P022020_45extensively drug-resistant strain Control
SA453585P022020_44extensively drug-resistant strain Control
SA453586P022020_43extensively drug-resistant strain Control
SA453587P022020_39extensively drug-resistant strain Control
SA453588022020_67extensively drug-resistant strain Control
SA453589P022020_31extensively drug-resistant strain Control
SA453590022020_62extensively drug-resistant strain Control
SA453591022020_27extensively drug-resistant strain Control
SA453592022020_45extensively drug-resistant strain Control
SA453593022020_44extensively drug-resistant strain Control
SA453594022020_43extensively drug-resistant strain Control
SA453595022020_39extensively drug-resistant strain Control
SA453596022020_38extensively drug-resistant strain Control
SA453597022020_37extensively drug-resistant strain Control
SA453598022020_33extensively drug-resistant strain Control
SA453599022020_32extensively drug-resistant strain Control
SA453600022020_31extensively drug-resistant strain Control
SA453601022020_26extensively drug-resistant strain Control
SA453602022020_50extensively drug-resistant strain Control
SA453603022020_25extensively drug-resistant strain Control
SA453604022020_20extensively drug-resistant strain Control
SA453605022020_19extensively drug-resistant strain Control
SA453606022020_15extensively drug-resistant strain Control
SA453607022020_14extensively drug-resistant strain Control
SA453608022020_13extensively drug-resistant strain Control
SA453609022020_09extensively drug-resistant strain Control
SA453610022020_08extensively drug-resistant strain Control
SA453611022020_07extensively drug-resistant strain Control
SA453612022020_49extensively drug-resistant strain Control
SA453613022020_21extensively drug-resistant strain Control
SA453614022020_51extensively drug-resistant strain Control
SA453615022020_56extensively drug-resistant strain Control
SA453616022020_57extensively drug-resistant strain Control
SA453617022020_55extensively drug-resistant strain Control
SA453618022020_61extensively drug-resistant strain Control
SA453619P022020_60extensively drug-resistant strain Trehalose
SA453620022020_18extensively drug-resistant strain Trehalose
SA453621P022020_66extensively drug-resistant strain Trehalose
SA453622P022020_65extensively drug-resistant strain Trehalose
SA453623P022020_64extensively drug-resistant strain Trehalose
SA453624022020_71extensively drug-resistant strain Trehalose
SA453625022020_72extensively drug-resistant strain Trehalose
SA453626022020_64extensively drug-resistant strain Trehalose
SA453627P022020_58extensively drug-resistant strain Trehalose
SA453628P022020_59extensively drug-resistant strain Trehalose
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Collection:

Collection ID:CO004103
Collection Summary:Mtb-laden filters were generated and incubated at 37°C for 5 days to reach mid-log phase of growth. To prepare for filter culture-based metabolomics, cultures on agar-supported filters were treated with trehalose. Mtb-laden filters were metabolically quenched by immersion in a precooled mixture of acetonitrile:methanol:H2O (40:40:20, v:v:v) at -40°C.
Collection Protocol Filename:methods.pdf
Sample Type:Bacterial cells

Treatment:

Treatment ID:TR004119
Treatment Summary:To prepare for filter culture-based metabolomics, cultures on agar-supported filters were treated with 20 mM trehalose.

Sample Preparation:

Sampleprep ID:SP004116
Sampleprep Summary:Mtb-laden filters were metabolically quenched by immersion in a precooled mixture of acetonitrile:methanol:H2O (40:40:20, v:v:v) at -40°C. Metabolites were extracted via mechanical lysis using 0.1-mm zirconia beads in a Precellys tissue homogenizer for 4 min at 6,000 rpm, repeated twice under continuous cooling at or below 2°C. The lysates were clarified by centrifugation and filtered through a 0.22-µm Spin-X column. The residual protein content was measured with a BCA protein assay kit (Thermo Scientific) to normalize metabolite levels to cell biomass.

Combined analysis:

Analysis ID AN006542 AN006543
Analysis type MS MS
Chromatography type Reversed phase Reversed phase
Chromatography system Agilent 6230 Agilent 6230
Column COGNET DIAMOND HYBRIDE 100A (150 x 2.1 mm, 4 µm) COGNET DIAMOND HYBRIDE 100A (150 x 2.1 mm, 4 µm)
MS Type ESI ESI
MS instrument type TOF TOF
MS instrument name Agilent 6230 TOF Agilent 6230 TOF
Ion Mode NEGATIVE POSITIVE
Units peak intensity peak intensity

Chromatography:

Chromatography ID:CH004964
Instrument Name:Agilent 6230
Column Name:COGNET DIAMOND HYBRIDE 100A (150 x 2.1 mm, 4 µm)
Column Temperature:25°C
Flow Gradient:0-2 min:85% B, 3-5 min: 80% B, 6-7 min:75% B, 8-9 min: 70% B, 10-11 min: 50% B, 11-14 min: 20% B, 14-24 min: 5% B
Flow Rate:0.4 mL/min
Solvent A:100% Water (ddH2O); 0.2% Formic acid
Solvent B:100% Acetonitrile; 0.2% Formic acid
Chromatography Type:Reversed phase

MS:

MS ID:MS006241
Analysis ID:AN006542
Instrument Name:Agilent 6230 TOF
Instrument Type:TOF
MS Type:ESI
MS Comments:The abundance of metabolites was analyzed with Agilent Qualitative Analysis B.07.00 and Profinder B.07.00 software (Agilent Technologies), employing a mass tolerance of < 0.005 Da.
Ion Mode:NEGATIVE
  
MS ID:MS006242
Analysis ID:AN006543
Instrument Name:Agilent 6230 TOF
Instrument Type:TOF
MS Type:ESI
MS Comments:The abundance of metabolites was analyzed with Agilent Qualitative Analysis B.07.00 and Profinder B.07.00 software (Agilent Technologies), employing a mass tolerance of < 0.005 Da.
Ion Mode:POSITIVE
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