Analysis of the oxidative stress regulon identifies soxS as a genetic target for resistance reversal in multi-drug resistant Klebsiella pneumoniae
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ABSTRACT:
PROVIDER: PRJNA612077 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR11292690.fastq.gz | Fastqsanger.gz | |||
| SRR11292691.fastq.gz | Fastqsanger.gz | |||
| SRR11292692.fastq.gz | Fastqsanger.gz | |||
| SRR11292693.fastq.gz | Fastqsanger.gz | |||
| SRR11292694.fastq.gz | Fastqsanger.gz |
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Project description:In bacteria the defence system to counter oxidative stress is orchestrated by three transcriptional factors – SoxS, SoxR and OxyR. Although the transcriptional regulon of these factors are known in many bacteria, similar data is not available for K. pneumoniae. To address this data gap, oxidative stress was induced in K. pneumoniae MGH 78578 using paraquat and the corresponding regulon was identified using RNA-seq. Since soxS was significantly induced , a soxS mutant was constructed to decipher this regulon in K. pneumoniae MGH75878. The ‘oxidative SoxS regulon’, comprising common genes differentially regulated genes in oxidative and soxS regulon was identified from both regulons – characterised a stringent group of genes which were regulated by SoxS during oxidative stress. Efflux pump encoding genes like acrAB-tolC, acrE along with marRABwere identified in the oxidative SoxS regulon. The phenotypic effect of the observed efflux pump regulation was confirmed in the soxS mutant that exhibited an 2 fold reduction in the minimum bactericidal concentration (MBC) against tetracycline compared to that of the isogenic wild type. Impaired efflux activity, allowing tetracycline to be accumulated in the cytoplasm to bactericidal levels, was further confirmed using tetraphenylphosphonium (TPP+) ion accumulation assay. The susceptibility of the soxS mutant against tetracycline was also apparent in vivo, in the zebrafish embryo model. We conclude that the soxS gene could be considered as a genetic target against which an inhibitor could be developed and be used in combinatorial therapy with tetracycline to combat infections associated with multi-drug resistant K. pneumoniae.
2021-05-26 | GSE146844 | GEO
Project description:Oxidative stress dependent regulon of AosR
| PRJNA675843 | ENA
Project description:Background: During gut colonization, the enteric pathogen C. jejuni has to surmount the toxic effects of reactive oxygen species produced by its own metabolism, by the host immune system and by the intestinal microflora. Elucidation of C. jejuni oxidative stress defense mechanisms is critical for understanding Campylobacter pathophysiology. Results: The mechanisms of oxidative stress defenses in Campylobacter jejuni were characterized by transcriptional profiling, genes mutagenesis, and phenotypic analysis. The transcriptome changes, in response to H2O2, cumene hydroperoxide, or menadione exposure, were found to be oxidant specific and revealed the differential expression of genes belonging to a variety of biological pathways, from the classical oxidative stress defense systems, to the heat shock response, DNA repair and metabolism, fatty acid and capsule biosynthesis, and multidrug efflux pumps. To define the peroxide sensing regulator PerR, an isogenic mutant was constructed and its transcriptome profile compared to the wild-type strain. Sixty-six genes were found to belong to the PerR regulon. PerR appear to regulate gene expression both dependently and independently of the presence of iron and/or H2O2. The perR mutant was affected in its motility and attenuated in the chick colonization model. Mutagenic and phenotypic studies of the superoxide disumutase SodB, the alkyl-hydroxyperoxidase AhpC, and the catalase KatA, revealed their role in oxidative stress defenses and chick gut colonization. Conclusion: This study reveals the interplay between PerR, the iron metabolism and the oxidative stress defenses and highlights their role in the colonization and/or survival of C. jejuni in the chick cecum. Keywords: Transcriptional response to 3 oxidants (H2O2, menadione and cumene hydroperoxide) and characterization of the perR regulon (comparison of the transciptomes from the wild-type and perR mutant).
2010-09-07 | GSE13126 | GEO
Project description:Background: During gut colonization, the enteric pathogen C. jejuni has to surmount the toxic effects of reactive oxygen species produced by its own metabolism, by the host immune system and by the intestinal microflora. Elucidation of C. jejuni oxidative stress defense mechanisms is critical for understanding Campylobacter pathophysiology. Results: The mechanisms of oxidative stress defenses in Campylobacter jejuni were characterized by transcriptional profiling, genes mutagenesis, and phenotypic analysis. The transcriptome changes, in response to H2O2, cumene hydroperoxide, or menadione exposure, were found to be oxidant specific and revealed the differential expression of genes belonging to a variety of biological pathways, from the classical oxidative stress defense systems, to the heat shock response, DNA repair and metabolism, fatty acid and capsule biosynthesis, and multidrug efflux pumps. To define the peroxide sensing regulator PerR, an isogenic mutant was constructed and its transcriptome profile compared to the wild-type strain. Sixty-six genes were found to belong to the PerR regulon. PerR appear to regulate gene expression both dependently and independently of the presence of iron and/or H2O2. The perR mutant was affected in its motility and attenuated in the chick colonization model. Mutagenic and phenotypic studies of the superoxide disumutase SodB, the alkyl-hydroxyperoxidase AhpC, and the catalase KatA, revealed their role in oxidative stress defenses and chick gut colonization. Conclusion: This study reveals the interplay between PerR, the iron metabolism and the oxidative stress defenses and highlights their role in the colonization and/or survival of C. jejuni in the chick cecum. Keywords: Transcriptional response to 3 oxidants (H2O2, menadione and cumene hydroperoxide) and characterization of the perR regulon (comparison of the transciptomes from the wild-type and perR mutant). To investigate the transcriptional responses of C. jejuni to oxidant exposure, hydrogen peroxide (H2O2), cumene hydroperoxide (CHP), or menadione sodium bisulfite (MND) was added to the 50 ml broth at a final concentration of 1 mM. The same amount of water or DMSO was added to the bacterial culture that served as reference samples for the transcriptional profile study in response to H2O2, MND or CHP. Furthermore, to investigate the transcriptional response of C. jejuni to H2O2 exposure in the presence of excess iron, ferrous sulfate was added to the bacterial culture at a final concentration of 40 µM, 15 min prior to H2O2 exposure. Ten minutes after the addition of the oxidant, total RNA was extracted and processed for microarray hybridization. To identify the PerR regulon, the wild-type strain C. jejuni NCTC 11168 and the perR mutant were grown in 500 ml flasks containing 250 ml of MEMα medium. At mid-log phase, 50 ml of the cultures were transferred to 100 ml flasks and ferrous sulfate and/or H2O2 were added . Ten minutes following the addition of H2O2 the cells were collected and the total RNA extracted.
2010-09-07 | E-GEOD-13126 | biostudies-arrayexpress
Project description:Oxidative stress that originates from reactive oxygen species (ROS) is an inevitable consequence of aerobic respiration in bacteria. Three transcription factors (TFs), OxyR, SoxR, and SoxS play a critical role in transcriptional regulation of the defense system. However, the full genome-wide regulatory potential of them remains elusive. Here, we comprehensively reconstruct genome-wide OxyR, SoxR, and SoxS transcriptional regulatory networks in Escherichia coli under oxidative stress. Integrative data analysis reveals that OxyR, SoxR, and SoxS regulons are comprised of 38 genes in 28 transcription units (TUs), 11 genes in 10 TUs, and 34 genes in 25 TUs, respectively, significantly expanding the current knowledge of their regulatory networks. Comparison of them to other stress-response regulatory networks highlights minimal overlap between their regulons, indicating that E. coli has a series of relatively distinct stress responses covering the range of different stresses. We also demonstrate that these intricate networks coordinate detoxification process with DNA and protein damage repair, cell wall synthesis, divalent metal ion homeostasis, as well as metabolic robustness to produce overall response of E. coli to oxidative stress.
2015-08-13 | GSE65711 | GEO
Project description:Oxidative stress that originates from reactive oxygen species (ROS) is an inevitable consequence of aerobic respiration in bacteria. Three transcription factors (TFs), OxyR, SoxR, and SoxS play a critical role in transcriptional regulation of the defense system. However, the full genome-wide regulatory potential of them remains elusive. Here, we comprehensively reconstruct genome-wide OxyR, SoxR, and SoxS transcriptional regulatory networks in Escherichia coli under oxidative stress. Integrative data analysis reveals that OxyR, SoxR, and SoxS regulons are comprised of 38 genes in 28 transcription units (TUs), 11 genes in 10 TUs, and 34 genes in 25 TUs, respectively, significantly expanding the current knowledge of their regulatory networks. Comparison of them to other stress-response regulatory networks highlights minimal overlap between their regulons, indicating that E. coli has a series of relatively distinct stress responses covering the range of different stresses. We also demonstrate that these intricate networks coordinate detoxification process with DNA and protein damage repair, cell wall synthesis, divalent metal ion homeostasis, as well as metabolic robustness to produce overall response of E. coli to oxidative stress.
2015-08-13 | GSE65710 | GEO
Project description:Oxidative stress that originates from reactive oxygen species (ROS) is an inevitable consequence of aerobic respiration in bacteria. Three transcription factors (TFs), OxyR, SoxR, and SoxS play a critical role in transcriptional regulation of the defense system. However, the full genome-wide regulatory potential of them remains elusive. Here, we comprehensively reconstruct genome-wide OxyR, SoxR, and SoxS transcriptional regulatory networks in Escherichia coli under oxidative stress. Integrative data analysis reveals that OxyR, SoxR, and SoxS regulons are comprised of 38 genes in 28 transcription units (TUs), 11 genes in 10 TUs, and 34 genes in 25 TUs, respectively, significantly expanding the current knowledge of their regulatory networks. Comparison of them to other stress-response regulatory networks highlights minimal overlap between their regulons, indicating that E. coli has a series of relatively distinct stress responses covering the range of different stresses. We also demonstrate that these intricate networks coordinate detoxification process with DNA and protein damage repair, cell wall synthesis, divalent metal ion homeostasis, as well as metabolic robustness to produce overall response of E. coli to oxidative stress. A total of six samples were analyzed. oxyR-8myc, soxR-8myc, and soxS-8myc tagged cells were cultured in M9 minimal media with 0.2% glucose. Then cells were treated with 250 uM of paraquat at mid-log pahse for 20 min with agitation.
2015-08-13 | E-GEOD-65710 | biostudies-arrayexpress
Project description:In this experiment, SUM149 IBC cells were cultured using baseline medium (N=3), and in baseline medium supplemented with increasing concentration of Lapatinib to induce resistance (N=3; rSUM149). Resistant reversal SUM149 cells (rrSUM149) were then generated by culturing in rSUM149 cells in baseline medium. Gene expression data were generated to identify differentially expressed genes, as well as differentially activated proteins and pathways during Lapatinib resistance and resistance reversal. Gene expression were also integrated with proteome expression data generated under the same conditions.
2024-04-05 | E-MTAB-13929 | biostudies-arrayexpress
Project description:The gastric human pathogen Helicobacter pylori has developed mechanisms to combat stress factors, including reactive oxygen species (ROS). Here, we present a comprehensive study on the redox switch protein HP1021 regulon combining transcriptomic, proteomic and DNA-protein interactions analyses. Our results indicated that HP1021 modulates H. pylori's response to oxidative stress. HP1021 controlled the transcription of 497 genes, including 407 genes related to response to oxidative stress. 79 proteins were differently expressed in the HP1021 deletion mutant. HP1021 regulated typical ROS response pathways (katA, rocF) and less canonical ones, particularly DNA uptake and central carbohydrate metabolism. We identified HP1021 as the first molecular regulator of competence in H. pylori, as HP1021-dependent repression of the comB DNA uptake genes was relieved under oxidative conditions, increasing natural competence. Furthermore, HP1021 controlled glucose consumption by directly regulating the gluP transporter and had an important impact on maintaining the energetic balance in the cell.
2023-09-20 | PXD041978 | Pride
Project description:Investigating the oxidative stress response: Candida glabrata strains were stressed with hydrogen peroxide and menadione (causing oxygen radicals) to induce the oxidative stress regulon, which is thought to be upregulated during the oxidative burst inside of phagocytic cells.
2011-01-01 | E-MEXP-2915 | biostudies-arrayexpress