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Title: Folate Pathway Disruption Leads to Critical Depletion of Methionine Derivatives in Mycobacterium tuberculosis      
dateReleased:
03-19-2014
description:
In this study, screening efforts identified novel antifolates with potent, targeted activity against whole cell Mycobacterium tuberculosis. Liquid chromatography-mass spectrometry analysis of antifolate-treated cultures revealed unique metabolic disruption, including decreased pools of methionine and S-adenosylmethionine. Transcriptomic analysis highlighted up-regulation genes involved in the biosynthesis and utilization of methionine. Supplementation with amino acids or methionine derivatives was sufficient to rescue cultures from MIC-level antifolate treatment. Instead of the “thymineless death” that characterizes folate pathway inhibition in a wide variety of organisms, these data suggest that M. tuberculosis is vulnerable to a critical disruption of the biosynthesis of methionine-derived compounds. These arrays look at the expression profile triggered by exposure to three different anti-folates (WR99210, dimethyl and diethyl methotrexate) in three biological replicates and in a matched set of untreated samples.
privacy:
not applicable
aggregation:
instance of dataset
ID:
E-GEOD-55979
refinement:
raw
alternateIdentifiers:
55979
keywords:
functional genomics
dateModified:
06-03-2014
availability:
available
types:
gene expression
name:
Mycobacterium tuberculosis H37Rv
ID:
A-GEOD-14824
name:
SBRI_MTuberculosis_12x130K_ver2.0
accessURL: https://www.ebi.ac.uk/arrayexpress/files/E-GEOD-55979/E-GEOD-55979.raw.1.zip
storedIn:
ArrayExpress
qualifier:
gzip compressed
format:
TXT
accessType:
download
authentication:
none
authorization:
none
accessURL: https://www.ebi.ac.uk/arrayexpress/files/E-GEOD-55979/E-GEOD-55979.processed.1.zip
storedIn:
ArrayExpress
qualifier:
gzip compressed
format:
TXT
accessType:
download
authentication:
none
authorization:
none
accessURL: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE55979
storedIn:
Gene Expression Omnibus
qualifier:
not compressed
format:
HTML
accessType:
landing page
primary:
true
authentication:
none
authorization:
none
abbreviation:
EBI
homePage: http://www.ebi.ac.uk/
ID:
SCR:004727
name:
European Bioinformatics Institute
homePage: https://www.ebi.ac.uk/arrayexpress/
ID:
SCR:002964
name:
ArrayExpress

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