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Series GSE56133 Query DataSets for GSE56133
Status Public on Apr 02, 2014
Title Antibiotics induce redox-related physiological alterations as part of their lethality
Platform organism Escherichia coli
Sample organism Escherichia coli str. K-12 substr. MG1655
Experiment type Expression profiling by array
Summary Deeper understanding of antibiotic-induced physiological responses is critical to identifying means for enhancing our current antibiotic arsenal. Bactericidal antibiotics with diverse targets have been hypothesized to kill bacteria, in part, by inducing production of damaging reactive species. This notion has been supported by many groups, but recently challenged. Here we robustly test the hypothesis using biochemical, enzymatic and biophysical assays along with genetic and phenotypic experiments. We first used a novel intracellular hydrogen peroxide (H2O2) sensor, together with a chemically diverse panel of fluorescent dyes sensitive to an array of reactive species, to demonstrate that antibiotics broadly induce redox stress. Subsequent gene expression analyses reveal that complex antibiotic-induced oxidative stress responses are distinct from canonical responses generated by supra-physiological levels of H2O2. We next developed a method to dynamically quantify cellular respiration and found that bactericidal antibiotics elevate oxygen consumption, indicating significant alterations to bacterial redox physiology. We further show that catalase or DNA mismatch repair enzyme overexpression, as well as antioxidant pre-treatment limit antibiotic lethality, indicating that reactive oxygen species causatively contribute to antibiotic killing. Critically, the killing efficacy of antibiotics was diminished under strict anaerobic conditions, but could be enhanced by exposure to molecular oxygen or addition of alternative electron acceptors, suggesting that environmental factors play a role in killing cells physiologically primed for death. This work provides direct evidence that bactericidal antibiotics, downstream of their target-specific interactions, induce complex redox alterations that contribute to cellular damage and death, thus supporting an evolving, expanded model of antibiotic lethality.
Here, we used microarrays to analyze oxidative stress responses to bactericidal antibiotic treatment in wildtype and mutant E coli
 
Overall design WT or mutant E coli cells were grown to OD ~0.3. Untreated cells were harvested at time 0 as controls. Treated cells given the appropriate chemical perturbation and harvested 1 hour post-treatment. All experiments were performed in technical triplicate.
 
Contributor(s) Yang JH, Dwyer DJ, Belenky P, Collins JJ, Walker GC
Citation(s) 24803433
NIH grant(s)
Grant ID Grant title Affiliation Name
R01 CA021615 Mutagenesis and Repair of DNA MASSACHUSETTS INSTITUTE OF TECHNOLOGY GRAHAM C WALKER
Submission date Mar 24, 2014
Last update date Mar 08, 2019
Contact name Jason H Yang
E-mail jasonhy@mit.edu
Organization name MIT / Broad Institute
Department Biological Engineering
Lab James Collins
Street address 415 Main St, Rm 2017
City Cambridge
State/province MA
ZIP/Postal code 02142
Country USA
 
Platforms (1)
GPL3154 [E_coli_2] Affymetrix E. coli Genome 2.0 Array
Samples (27)
GSM1356325 WT Untreated 1
GSM1356326 WT Untreated 2
GSM1356327 WT Untreated 3
Relations
BioProject PRJNA242527

Download family Format
SOFT formatted family file(s) SOFTHelp
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Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE56133_RAW.tar 24.4 Mb (http)(custom) TAR (of CEL)
SRA Run SelectorHelp
Raw data provided as supplementary file
Processed data included within Sample table

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