Summary of Study ST003969

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 PR002485. The data can be accessed directly via it's Project DOI: 10.21228/M8F25H 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	ST003969
Study Title	Effect of Desiccation of Mycobacterium tuberculosis metabolism
Study Type	Metabolomics
Study Summary	Mycobacterium tuberculosis (Mtb) is an obligate human pathogen that depends on its ability to spread from host-to-host to survive as a species. Yet, knowledge of transmission-specific traits remains lacking. Here, we report the discovery of a specific adaptive response to desiccation, a stress intrinsically linked to the generation of the aerosol droplets within which Mtb transmits. We show that desiccation inflicts oxidative damage and activates Mtb’s DNA repair responses but that this repair is imperfect and results in mutations. We further show that activation of these DNA repair responses is accompanied by increased expression of the transcription-coupled repair factor, mfd, but that this expression serves to buffer the fitness cost of specific resistance-conferring mutations in rpoB, the target of the frontline drug rifampin, rather than to facilitate transcription-coupled DNA repair. Silencing mfd during aerosolization impairs survival of strains harboring the rifampin resistance allele S450L. This function is further supported by whole genome sequence data from over 50,000 clinically circulating strains. These studies indicate that Mtb has evolved transmission-specific stress responses that have enabled it to leverage desiccation-induced DNA damage as a potential source of genetic diversification and drug resistance.
Institute	Weill Cornell Medicine
Department	Department of Medicine, Division of Infectious Diseases
Laboratory	Rhee Lab
Last Name	Brown
First Name	Christopher
Address	413 E 69th St
Email	cdb9006@med.cornell.edu
Phone	16469626225
Submit Date	2025-06-08
Num Groups	5
Publications	https://doi.org/10.1101/2025.06.04.657859
Raw Data Available	Yes
Raw Data File Type(s)	d, mxXML
Analysis Type Detail	LC-MS
Release Date	2025-07-07
Release Version	1

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Project:

Project ID:	PR002485
Project DOI:	doi: 10.21228/M8F25H
Project Title:	Effect of Desiccation of Mycobacterium tuberculosis metabolism
Project Summary:	The goal of this project was to measure metabolite shifts in Mycobacterium tuberculosis (Mtb) in response to desiccation and rehydration. We characterized the metabolome of Mtb in log phase and compared it to cells that were either dried for 24 hours or held in a solution of 200 mM sodium chloride. Following this incubation cells were rehydrated into 200 mM sodium chloride. We performed targeted metabolomics on each of these conditions using LC-MS. Significant increases in oxidized nucleotides and intermediates of de novo nucleotide biosynthesis were discovered in the desiccated samples. These metaboite accumulations reversed with rehydration.
Institute:	Weill Cornell Medicine
Department:	Department of Medicine, Division of Infectious Diseases
Laboratory:	Rhee Lab
Last Name:	Brown
First Name:	Christopher
Address:	413 E 69th St, New York, NY, 10021, USA
Email:	cdb9006@med.cornell.edu
Phone:	6469626225
Funding Source:	P01AI159402 (PI: Rhee)
Publications:	https://doi.org/10.1101/2025.06.04.657859

Subject:

Subject ID:	SU004106
Subject Type:	Bacteria
Subject Species:	Mycobacterium tuberculosis (H37Rv)
Taxonomy ID:	83332
Genotype Strain:	H37Rv

Factors:

Subject type: Bacteria; Subject species: Mycobacterium tuberculosis (H37Rv) (Factor headings shown in green)

mb_sample_id	local_sample_id	Sample source	Growth condition
SA453096	051823_POS_RH70_D13	Mycobacterium tuberculosis H37Rv grown in vitro	24 hours of desiccation from biofilm
SA453097	20220422_RNAseq_D12_Hilic_January_Neg	Mycobacterium tuberculosis H37Rv grown in vitro	24 hours of desiccation from biofilm
SA453098	20220422_RNAseq_D13_Hilic_January_Neg	Mycobacterium tuberculosis H37Rv grown in vitro	24 hours of desiccation from biofilm
SA453099	051823_NEG_RH70_D13	Mycobacterium tuberculosis H37Rv grown in vitro	24 hours of desiccation from biofilm
SA453100	051823_NEG_RH70_D12	Mycobacterium tuberculosis H37Rv grown in vitro	24 hours of desiccation from biofilm
SA453101	051823_NEG_RH70_D11	Mycobacterium tuberculosis H37Rv grown in vitro	24 hours of desiccation from biofilm
SA453102	20220329_RNAseq_D11_FA_March22_Pos	Mycobacterium tuberculosis H37Rv grown in vitro	24 hours of desiccation from biofilm
SA453103	20220329_RNAseq_D12_FA_March22_Pos	Mycobacterium tuberculosis H37Rv grown in vitro	24 hours of desiccation from biofilm
SA453104	20220329_RNAseq_D13_FA_March22_Pos	Mycobacterium tuberculosis H37Rv grown in vitro	24 hours of desiccation from biofilm
SA453105	20220422_RNAseq_D11_Hilic_January_Neg	Mycobacterium tuberculosis H37Rv grown in vitro	24 hours of desiccation from biofilm
SA453106	051823_POS_RH70_D12	Mycobacterium tuberculosis H37Rv grown in vitro	24 hours of desiccation from biofilm
SA453107	20250113_Hilic_RH70_D11	Mycobacterium tuberculosis H37Rv grown in vitro	24 hours of desiccation from biofilm
SA453108	20250113_Hilic_RH70_D12	Mycobacterium tuberculosis H37Rv grown in vitro	24 hours of desiccation from biofilm
SA453109	20250113_Hilic_RH70_D13	Mycobacterium tuberculosis H37Rv grown in vitro	24 hours of desiccation from biofilm
SA453110	051823_POS_RH70_D11	Mycobacterium tuberculosis H37Rv grown in vitro	24 hours of desiccation from biofilm
SA453111	20220329_RNAseq_D13_FA_March22_Neg	Mycobacterium tuberculosis H37Rv grown in vitro	24 hours of desiccation from biofilm
SA453112	20220329_RNAseq_D12_FA_March22_Neg	Mycobacterium tuberculosis H37Rv grown in vitro	24 hours of desiccation from biofilm
SA453113	20220329_RNAseq_D11_FA_March22_Neg	Mycobacterium tuberculosis H37Rv grown in vitro	24 hours of desiccation from biofilm
SA453114	051823_NEG_RH70_W12	Mycobacterium tuberculosis H37Rv grown in vitro	24 hours of incubation in 200 mM NaCl
SA453115	051823_POS_RH70_W12	Mycobacterium tuberculosis H37Rv grown in vitro	24 hours of incubation in 200 mM NaCl
SA453116	20220329_RNAseq_W11_FA_March22_Pos	Mycobacterium tuberculosis H37Rv grown in vitro	24 hours of incubation in 200 mM NaCl
SA453117	051823_POS_RH70_W13	Mycobacterium tuberculosis H37Rv grown in vitro	24 hours of incubation in 200 mM NaCl
SA453118	051823_NEG_RH70_W13	Mycobacterium tuberculosis H37Rv grown in vitro	24 hours of incubation in 200 mM NaCl
SA453119	20220329_RNAseq_W12_FA_March22_Pos	Mycobacterium tuberculosis H37Rv grown in vitro	24 hours of incubation in 200 mM NaCl
SA453120	051823_POS_RH70_W11	Mycobacterium tuberculosis H37Rv grown in vitro	24 hours of incubation in 200 mM NaCl
SA453121	20220422_RNAseq_W11_Hilic_January_Neg	Mycobacterium tuberculosis H37Rv grown in vitro	24 hours of incubation in 200 mM NaCl
SA453122	051823_NEG_RH70_W11	Mycobacterium tuberculosis H37Rv grown in vitro	24 hours of incubation in 200 mM NaCl
SA453123	20220329_RNAseq_W12_FA_March22_Neg	Mycobacterium tuberculosis H37Rv grown in vitro	24 hours of incubation in 200 mM NaCl
SA453124	20250113_Hilic_RH70_W13	Mycobacterium tuberculosis H37Rv grown in vitro	24 hours of incubation in 200 mM NaCl
SA453125	20250113_Hilic_RH70_W12	Mycobacterium tuberculosis H37Rv grown in vitro	24 hours of incubation in 200 mM NaCl
SA453126	20250113_Hilic_RH70_W11	Mycobacterium tuberculosis H37Rv grown in vitro	24 hours of incubation in 200 mM NaCl
SA453127	20220329_RNAseq_W11_FA_March22_Neg	Mycobacterium tuberculosis H37Rv grown in vitro	24 hours of incubation in 200 mM NaCl
SA453128	20220329_RNAseq_W13_FA_March22_Neg	Mycobacterium tuberculosis H37Rv grown in vitro	24 hours of incubation in 200 mM NaCl
SA453129	20220422_RNAseq_W13_Hilic_January_Neg	Mycobacterium tuberculosis H37Rv grown in vitro	24 hours of incubation in 200 mM NaCl
SA453130	20220422_RNAseq_W12_Hilic_January_Neg	Mycobacterium tuberculosis H37Rv grown in vitro	24 hours of incubation in 200 mM NaCl
SA453131	20220329_RNAseq_W13_FA_March22_Pos	Mycobacterium tuberculosis H37Rv grown in vitro	24 hours of incubation in 200 mM NaCl
SA453132	20250113_Hilic_RH70_D01	Mycobacterium tuberculosis H37Rv grown in vitro	Log phase biofilm growth on 7H10
SA453133	20250113_Hilic_RH70_D02	Mycobacterium tuberculosis H37Rv grown in vitro	Log phase biofilm growth on 7H10
SA453134	20220422_RNAseq_D03_Hilic_January_Neg	Mycobacterium tuberculosis H37Rv grown in vitro	Log phase biofilm growth on 7H10
SA453135	20250113_Hilic_RH70_D03	Mycobacterium tuberculosis H37Rv grown in vitro	Log phase biofilm growth on 7H10
SA453136	20220422_RNAseq_D01_Hilic_January_Neg	Mycobacterium tuberculosis H37Rv grown in vitro	Log phase biofilm growth on 7H10
SA453137	051823_POS_RH70_D03	Mycobacterium tuberculosis H37Rv grown in vitro	Log phase biofilm growth on 7H10
SA453138	20220422_RNAseq_D02_Hilic_January_Neg	Mycobacterium tuberculosis H37Rv grown in vitro	Log phase biofilm growth on 7H10
SA453139	051823_POS_RH70_D02	Mycobacterium tuberculosis H37Rv grown in vitro	Log phase biofilm growth on 7H10
SA453140	20220329_RNAseq_D01_FA_March22_Neg	Mycobacterium tuberculosis H37Rv grown in vitro	Log phase biofilm growth on 7H10
SA453141	20220329_RNAseq_D02_FA_March22_Neg	Mycobacterium tuberculosis H37Rv grown in vitro	Log phase biofilm growth on 7H10
SA453142	20220329_RNAseq_D03_FA_March22_Pos	Mycobacterium tuberculosis H37Rv grown in vitro	Log phase biofilm growth on 7H10
SA453143	20220329_RNAseq_D03_FA_March22_Neg	Mycobacterium tuberculosis H37Rv grown in vitro	Log phase biofilm growth on 7H10
SA453144	051823_NEG_RH70_D01	Mycobacterium tuberculosis H37Rv grown in vitro	Log phase biofilm growth on 7H10
SA453145	051823_NEG_RH70_D02	Mycobacterium tuberculosis H37Rv grown in vitro	Log phase biofilm growth on 7H10
SA453146	051823_NEG_RH70_D03	Mycobacterium tuberculosis H37Rv grown in vitro	Log phase biofilm growth on 7H10
SA453147	20220329_RNAseq_D01_FA_March22_Pos	Mycobacterium tuberculosis H37Rv grown in vitro	Log phase biofilm growth on 7H10
SA453148	20220329_RNAseq_D02_FA_March22_Pos	Mycobacterium tuberculosis H37Rv grown in vitro	Log phase biofilm growth on 7H10
SA453149	051823_POS_RH70_D01	Mycobacterium tuberculosis H37Rv grown in vitro	Log phase biofilm growth on 7H10
SA453150	051823_POS_RH70_RW2	Mycobacterium tuberculosis H37Rv grown in vitro	Rehydration into 200 mM NaCl after 24 hours in 200 mM NaCl
SA453151	20250113_Hilic_RH70_RW1	Mycobacterium tuberculosis H37Rv grown in vitro	Rehydration into 200 mM NaCl after 24 hours in 200 mM NaCl
SA453152	20220329_RNAseq_RW3_FA_March22_Neg	Mycobacterium tuberculosis H37Rv grown in vitro	Rehydration into 200 mM NaCl after 24 hours in 200 mM NaCl
SA453153	20220329_RNAseq_RW1_FA_March22_Pos	Mycobacterium tuberculosis H37Rv grown in vitro	Rehydration into 200 mM NaCl after 24 hours in 200 mM NaCl
SA453154	051823_POS_RH70_RW3	Mycobacterium tuberculosis H37Rv grown in vitro	Rehydration into 200 mM NaCl after 24 hours in 200 mM NaCl
SA453155	20220422_RNAseq_RW3_Hilic_January_Neg	Mycobacterium tuberculosis H37Rv grown in vitro	Rehydration into 200 mM NaCl after 24 hours in 200 mM NaCl
SA453156	20220422_RNAseq_RW2_Hilic_January_Neg	Mycobacterium tuberculosis H37Rv grown in vitro	Rehydration into 200 mM NaCl after 24 hours in 200 mM NaCl
SA453157	20220422_RNAseq_RW1_Hilic_January_Neg	Mycobacterium tuberculosis H37Rv grown in vitro	Rehydration into 200 mM NaCl after 24 hours in 200 mM NaCl
SA453158	20220329_RNAseq_RW3_FA_March22_Pos	Mycobacterium tuberculosis H37Rv grown in vitro	Rehydration into 200 mM NaCl after 24 hours in 200 mM NaCl
SA453159	20220329_RNAseq_RW1_FA_March22_Neg	Mycobacterium tuberculosis H37Rv grown in vitro	Rehydration into 200 mM NaCl after 24 hours in 200 mM NaCl
SA453160	20220329_RNAseq_RW2_FA_March22_Neg	Mycobacterium tuberculosis H37Rv grown in vitro	Rehydration into 200 mM NaCl after 24 hours in 200 mM NaCl
SA453161	20250113_Hilic_RH70_RW2	Mycobacterium tuberculosis H37Rv grown in vitro	Rehydration into 200 mM NaCl after 24 hours in 200 mM NaCl
SA453162	051823_NEG_RH70_RW1	Mycobacterium tuberculosis H37Rv grown in vitro	Rehydration into 200 mM NaCl after 24 hours in 200 mM NaCl
SA453163	051823_NEG_RH70_RW2	Mycobacterium tuberculosis H37Rv grown in vitro	Rehydration into 200 mM NaCl after 24 hours in 200 mM NaCl
SA453164	051823_NEG_RH70_RW3	Mycobacterium tuberculosis H37Rv grown in vitro	Rehydration into 200 mM NaCl after 24 hours in 200 mM NaCl
SA453165	20250113_Hilic_RH70_RW3	Mycobacterium tuberculosis H37Rv grown in vitro	Rehydration into 200 mM NaCl after 24 hours in 200 mM NaCl
SA453166	051823_POS_RH70_RW1	Mycobacterium tuberculosis H37Rv grown in vitro	Rehydration into 200 mM NaCl after 24 hours in 200 mM NaCl
SA453167	20220329_RNAseq_RW2_FA_March22_Pos	Mycobacterium tuberculosis H37Rv grown in vitro	Rehydration into 200 mM NaCl after 24 hours in 200 mM NaCl
SA453168	20220329_RNAseq_RD2_FA_March22_Neg	Mycobacterium tuberculosis H37Rv grown in vitro	Rehydration into 200 mM NaCl after 24 hours of desiccation
SA453169	20250113_Hilic_RH70_RD2	Mycobacterium tuberculosis H37Rv grown in vitro	Rehydration into 200 mM NaCl after 24 hours of desiccation
SA453170	20250113_Hilic_RH70_RD1	Mycobacterium tuberculosis H37Rv grown in vitro	Rehydration into 200 mM NaCl after 24 hours of desiccation
SA453171	20220329_RNAseq_RD3_FA_March22_Neg	Mycobacterium tuberculosis H37Rv grown in vitro	Rehydration into 200 mM NaCl after 24 hours of desiccation
SA453172	20220329_RNAseq_RD1_FA_March22_Neg	Mycobacterium tuberculosis H37Rv grown in vitro	Rehydration into 200 mM NaCl after 24 hours of desiccation
SA453173	20250113_Hilic_RH70_RD3	Mycobacterium tuberculosis H37Rv grown in vitro	Rehydration into 200 mM NaCl after 24 hours of desiccation
SA453174	051823_NEG_RH70_RD1	Mycobacterium tuberculosis H37Rv grown in vitro	Rehydration into 200 mM NaCl after 24 hours of desiccation
SA453175	20220329_RNAseq_RD3_FA_March22_Pos	Mycobacterium tuberculosis H37Rv grown in vitro	Rehydration into 200 mM NaCl after 24 hours of desiccation
SA453176	051823_POS_RH70_RD1	Mycobacterium tuberculosis H37Rv grown in vitro	Rehydration into 200 mM NaCl after 24 hours of desiccation
SA453177	051823_NEG_RH70_RD2	Mycobacterium tuberculosis H37Rv grown in vitro	Rehydration into 200 mM NaCl after 24 hours of desiccation
SA453178	20220422_RNAseq_RD2_Hilic_January_Neg	Mycobacterium tuberculosis H37Rv grown in vitro	Rehydration into 200 mM NaCl after 24 hours of desiccation
SA453179	20220422_RNAseq_RD1_Hilic_January_Neg	Mycobacterium tuberculosis H37Rv grown in vitro	Rehydration into 200 mM NaCl after 24 hours of desiccation
SA453180	051823_NEG_RH70_RD3	Mycobacterium tuberculosis H37Rv grown in vitro	Rehydration into 200 mM NaCl after 24 hours of desiccation
SA453181	051823_POS_RH70_RD2	Mycobacterium tuberculosis H37Rv grown in vitro	Rehydration into 200 mM NaCl after 24 hours of desiccation
SA453182	051823_POS_RH70_RD3	Mycobacterium tuberculosis H37Rv grown in vitro	Rehydration into 200 mM NaCl after 24 hours of desiccation
SA453183	20220329_RNAseq_RD1_FA_March22_Pos	Mycobacterium tuberculosis H37Rv grown in vitro	Rehydration into 200 mM NaCl after 24 hours of desiccation
SA453184	20220329_RNAseq_RD2_FA_March22_Pos	Mycobacterium tuberculosis H37Rv grown in vitro	Rehydration into 200 mM NaCl after 24 hours of desiccation
SA453185	20220422_RNAseq_RD3_Hilic_January_Neg	Mycobacterium tuberculosis H37Rv grown in vitro	Rehydration into 200 mM NaCl after 24 hours of desiccation

Showing results 1 to 90 of 90

Showing results 1 to 90 of 90

Collection:

Collection ID:	CO004099
Collection Summary:	Laboratory strain H37Rv was grown as a biofilm on Middlebrook 7H10 agar supplemented with glucose, sodium chloride, fatty-acid free albumin and glycerol. Cells were plunged into a 40/40/20 mixture of methanol, acetonitrile and mili-Q water followed by lysis. Stored at -80 C until analysis by LC-MS.
Sample Type:	Cultured cells
Storage Conditions:	-80℃

Treatment:

Treatment ID:	TR004115
Treatment Summary:	We analyzed the effect of desiccation on Mycobacterium tuberculosis (Mtb) metabolism. Laboratory strain H37Rv was grown as a biofilm on Middlebrook 7H10 agar supplemented with glucose, sodium chloride, fatty-acid free albumin and glycerol. Biofilms were incubated for 24 hours at 37 °C in 70% relative humidity over liquid reservoirs containing 200 mM NaCl (wet condition) or left empty (dry condition). Following 24 hours, wet and dry conditions were rehydrated in 200 mM NaCl and incubated a further 24 hours. Each experiment included 3 biological replicates and was performed twice. LC-MS metabolomics revealed significant changes to central and secondary carbon metabolism.

Treatment ID:

TR004115

Treatment Summary:

We analyzed the effect of desiccation on Mycobacterium tuberculosis (Mtb) metabolism. Laboratory strain H37Rv was grown as a biofilm on Middlebrook 7H10 agar supplemented with glucose, sodium chloride, fatty-acid free albumin and glycerol. Biofilms were incubated for 24 hours at 37 °C in 70% relative humidity over liquid reservoirs containing 200 mM NaCl (wet condition) or left empty (dry condition). Following 24 hours, wet and dry conditions were rehydrated in 200 mM NaCl and incubated a further 24 hours. Each experiment included 3 biological replicates and was performed twice. LC-MS metabolomics revealed significant changes to central and secondary carbon metabolism.

Sample Preparation:

Sampleprep ID:	SP004112
Sampleprep Summary:	Cell-laden filters were plunged into 2 mL screw cap threaded tubes with O-ring seal (Sarstedt) containing 1mL of a 2:2:1 HPLC-grade Methanol:acetonitrile:water (Sigma-Aldrich) solution. Cells were lysed in an air-chilled Precellys homogenizer at 6000 rpm x 3 cycles x 30 seconds per cycle with 30 seconds rest in between to prevent sample overheating. Lysates were filtered through a 0.22 µm column to ensure sterilization before removal from BSL3 laboratory. 100 µL aliquot of lysate was combined with 100 µL of ddH2O containing 0.2% formic acid and centrifuged. The supernatant was analyzed by LC-MS.

Sampleprep ID:

SP004112

Sampleprep Summary:

Cell-laden filters were plunged into 2 mL screw cap threaded tubes with O-ring seal (Sarstedt) containing 1mL of a 2:2:1 HPLC-grade Methanol:acetonitrile:water (Sigma-Aldrich) solution. Cells were lysed in an air-chilled Precellys homogenizer at 6000 rpm x 3 cycles x 30 seconds per cycle with 30 seconds rest in between to prevent sample overheating. Lysates were filtered through a 0.22 µm column to ensure sterilization before removal from BSL3 laboratory. 100 µL aliquot of lysate was combined with 100 µL of ddH2O containing 0.2% formic acid and centrifuged. The supernatant was analyzed by LC-MS.

Chromatography:

Chromatography ID:	CH004957
Chromatography Summary:	The metabolite admixture was chromatographically separated using hydrophilic interaction chromatography (HILIC)on a Poroshell 120 Hilic-Z column (150 mm) using a gradient mobile phase (flow rate 0.25 mL/min) composed of Solvent A (10mM ammonium acetate in ddH2O with 5 µM Infinity Lab deactivator (Agilent)) and Solvent B (95:15 Acetonitrile:ddH2O with 10 mM ammonium acetate and 5 µM Infinity Lab deactivator). Starting composition of solvents was 4% Solvent A and 96% Solvent B and rising to 35% Solvent A and 65% Solvent B over 24 minutes.
Instrument Name:	Agilent QTOF
Column Name:	Agilent Infinity Lab Poroshell 120 Hilic-Z (150 x 2.1mm, 2.7um)
Column Temperature:	25 C
Flow Gradient:	96% B to 65% B linear gradient over 24 minutes
Flow Rate:	0.25 mL/min
Solvent A:	100% water; 10mM ammonium acetate; 5 µM Infinity Lab deactivator (Agilent)
Solvent B:	85% Acetonitrile/15% water; 10 mM ammonium acetate; 5 µM Infinity Lab deactivator
Chromatography Type:	HILIC

Analysis:

Analysis ID:	AN006530
Analysis Type:	MS
Chromatography ID:	CH004957
Num Factors:	5
Num Metabolites:	7
Rt Units:	Minutes
Units:	AUC/CFU per mL