Dataset Information

DNA microarray-mediated transcriptional profiling of the Escherichia coli response to hydrogen peroxide.

ABSTRACT: The genome-wide transcription profile of Escherichia coli cells treated with hydrogen peroxide was examined with a DNA microarray composed of 4,169 E. coli open reading frames. By measuring gene expression in isogenic wild-type and oxyR deletion strains, we confirmed that the peroxide response regulator OxyR activates most of the highly hydrogen peroxide-inducible genes. The DNA microarray measurements allowed the identification of several new OxyR-activated genes, including the hemH heme biosynthetic gene; the six-gene suf operon, which may participate in Fe-S cluster assembly or repair; and four genes of unknown function. We also identified several genes, including uxuA, encoding mannonate hydrolase, whose expression might be repressed by OxyR, since their expression was elevated in the DeltaoxyR mutant strain. In addition, the induction of some genes was found to be OxyR independent, indicating the existence of other peroxide sensors and regulators in E. coli. For example, the isc operon, which specifies Fe-S cluster formation and repair activities, was induced by hydrogen peroxide in strains lacking either OxyR or the superoxide response regulators SoxRS. These results expand our understanding of the oxidative stress response and raise interesting questions regarding the nature of other regulators that modulate gene expression in response to hydrogen peroxide.

SUBMITTER: Zheng M

PROVIDER: S-EPMC95351 | biostudies-literature | 2001 Aug

REPOSITORIES: biostudies-literature

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DNA microarray-mediated transcriptional profiling of the Escherichia coli response to hydrogen peroxide.

Zheng M M Wang X X Templeton L J LJ Smulski D R DR LaRossa R A RA Storz G G

Journal of bacteriology 20010801 15

The genome-wide transcription profile of Escherichia coli cells treated with hydrogen peroxide was examined with a DNA microarray composed of 4,169 E. coli open reading frames. By measuring gene expression in isogenic wild-type and oxyR deletion strains, we confirmed that the peroxide response regulator OxyR activates most of the highly hydrogen peroxide-inducible genes. The DNA microarray measurements allowed the identification of several new OxyR-activated genes, including the hemH heme biosyn ...[more]

PMID: 11443091

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Project description:Hydrogen peroxide (H2O2) is used by phagocytic cells of the innate immune response to kill engulfed bacteria. H2O2 diffuses freely into bacteria, where it can wreak havoc on sensitive biomolecules if it is not rapidly detoxified. Accordingly, bacteria have evolved numerous systems to defend themselves against H2O2, and the importance of these systems to pathogenesis has been substantiated by the many bacteria that require them to establish or sustain infections. The kinetic competition for H2O2 within bacteria is complex, which suggests that quantitative models will improve interpretation and prediction of network behavior. To date, such models have been of limited scope, and this inspired us to construct a quantitative, systems-level model of H2O2 detoxification in Escherichia coli that includes detoxification enzymes, H2O2-dependent transcriptional regulation, enzyme degradation, the Fenton reaction and damage caused by •OH, oxidation of biomolecules by H2O2, and repair processes. After using an iterative computational and experimental procedure to train the model, we leveraged it to predict how H2O2 detoxification would change in response to an environmental perturbation that pathogens encounter within host phagosomes, carbon source deprivation, which leads to translational inhibition and limited availability of NADH. We found that the model accurately predicted that NADH depletion would delay clearance at low H2O2 concentrations and that detoxification at higher concentrations would resemble that of carbon-replete conditions. These results suggest that protein synthesis during bolus H2O2 stress does not affect clearance dynamics and that access to catabolites only matters at low H2O2 concentrations. We anticipate that this model will serve as a computational tool for the quantitative exploration and dissection of oxidative stress in bacteria, and that the model and methods used to develop it will provide important templates for the generation of comparable models for other bacterial species.

Dataset Information

DNA microarray-mediated transcriptional profiling of the Escherichia coli response to hydrogen peroxide.

Publications

DNA microarray-mediated transcriptional profiling of the Escherichia coli response to hydrogen peroxide.

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