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Altering gene expression by aminocoumarin (novobiocin) treatment: Role of DNA supercoiling in Staphylococcus aureus

ABSTRACT: For Staphylococcus aureus it was shown previously that aminocoumarinecoumarin antibiotics such as novobiocin lead to immediate down-regulation of recA expression and thereby inhibition of the SOS response, the mutation frequency and the recombination capacity. Aminocoumarinecoumarin function by inhibition of the ATPase activity of the gyrase subunit B. Here we analysed the global impact of the DNA relaxing agent novobiocin on gene expression in S. aureus. By use of a novobiocin resistant mutant, it became evident that the change in recA expression is due to gyrase inhibition. Microarray analysis and Northern blot hybridization revealed that the expression of a distinct set of genes is increased (e.g. recF-gyrB-gyrA, rib operon and ure operon …)), or decreased (e.g. arlRS, recA, lukA, hlgC, fnbA) by novobiocin. The two-component ArlRS system was previously found to decrease the supercoiling level in S. aureus. Thus, down-regulation of arlRS might in part compensate for the relaxing effect of novobiocin. Novobiocin resulted in down-regulation of several of arlRS repressed target genes in an arl mutant. Global analysis and gene mapping of supercoiling sensitive genes did not give indications that they are clustered in the genome. Promoter fusion assays confirmed that responsiveness of a given gene is intrinsic to the promoter region but independent of the chromosomal location. The results indicate that molecular property of the spacers of a given promoter dictatesa given promoter rather than chromosomal topology dictates the responsiveness towards changes in supercoiling rather than chromosomal topology.

ORGANISM(S): Staphylococcus aureus

PROVIDER: GSE50157 | GEO | 2014/09/08

SECONDARY ACCESSION(S): PRJNA216920

REPOSITORIES: GEO

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Altering gene expression by aminocoumarin (novobiocin) treatment: Role of DNA supercoiling in Staphylococcus aureus

Project description:For Staphylococcus aureus it was shown previously that aminocoumarinecoumarin antibiotics such as novobiocin lead to immediate down-regulation of recA expression and thereby inhibition of the SOS response, the mutation frequency and the recombination capacity. Aminocoumarinecoumarin function by inhibition of the ATPase activity of the gyrase subunit B. Here we analysed the global impact of the DNA relaxing agent novobiocin on gene expression in S. aureus. By use of a novobiocin resistant mutant, it became evident that the change in recA expression is due to gyrase inhibition. Microarray analysis and Northern blot hybridization revealed that the expression of a distinct set of genes is increased (e.g. recF-gyrB-gyrA, rib operon and ure operon M-bM-^@M-&)), or decreased (e.g. arlRS, recA, lukA, hlgC, fnbA) by novobiocin. The two-component ArlRS system was previously found to decrease the supercoiling level in S. aureus. Thus, down-regulation of arlRS might in part compensate for the relaxing effect of novobiocin. Novobiocin resulted in down-regulation of several of arlRS repressed target genes in an arl mutant. Global analysis and gene mapping of supercoiling sensitive genes did not give indications that they are clustered in the genome. Promoter fusion assays confirmed that responsiveness of a given gene is intrinsic to the promoter region but independent of the chromosomal location. The results indicate that molecular property of the spacers of a given promoter dictatesa given promoter rather than chromosomal topology dictates the responsiveness towards changes in supercoiling rather than chromosomal topology. We analyzed S. aureus global gene expression changes to the treatment of novobiocin

2014-09-08 | E-GEOD-50157 | biostudies-arrayexpress

Transcriptomic response of Dickeya dadantii to DNA relaxation by novobiocin

Project description:We analyze the transcriptomic response of the phytopathogenic enterobacterium Dickeya dadantii to a DNA supercoiling relaxation shock using the gyrase inhibitor novobiocin. The shock was applied to Dickeya cells grown in minimal medium supplemented with sucrose, in exponential or transition to stationary phase, and in minimal medium with sucrose + PGA (a pectin derivative) in transition to stationary phase.

2019-04-16 | E-MTAB-7650 | biostudies-arrayexpress

Transcriptomic response of Dickeya dadantii ihfA mutant to DNA relaxation by novobiocin

Project description:We analyze the transcriptomic response of the phytopathogenic enterobacterium Dickeya dadantii ihfA mutant to a DNA supercoiling relaxation shock using the gyrase inhibitor novobiocin. The shock was applied to Dickeya cells grown in minimal medium supplemented with sucrose, in exponential or transition to stationary phase, and in minimal medium with sucrose + PGA (a pectin derivative) in transition to stationary phase.

2021-02-10 | E-MTAB-9025 | biostudies-arrayexpress

Symmetric Bis-benzimidazoles Are Potent Anti-Staphylococcal Agents with Dual Inhibitory Mechanisms against DNA Gyrase

Project description:Various bis-benzimidazole derivatives have been reported to possess activity against Gram-positive pathogens. No mechanism of action has been elucidated to fully account for the antibacterial activity of this class of compounds. A group of symmetric bis-benzimidazoles (BBZ) designed as anticancer agents have previously been shown to possess moderate antiproliferative activity. We sought to assess the antibacterial activity and mechanism of action of BBZ compounds against Staphylococcus aureus. Antibacterial activities were assessed by determination of minimal inhibitory concentrations (MICs), time-kill curves, and scanning electron microscopy. Transcriptional responses to BBZ treatment were determined using whole genome microarrays. Activities against bacterial type II topoisomerases were investigated using in vitro supercoiling, decatenation, DNA binding, and DNA cleavage inhibition assays. MICs for EMRSA-16 were between 0.03 and 0.5 μg/mL. The compounds showed concentration-dependent bactericidal activity and induced cell swelling and lysis. Transcriptional responses to BBZ were consistent with topoisomerase inhibition and DNA damage. A subset of BBZ compounds inhibited S. aureus DNA gyrase supercoiling activity with IC50 values in the range of 5−10 μM. This inhibition was subsequently shown to operate through both inhibition of binding of DNA gyrase to DNA and accumulation of single-stranded DNA breaks. We conclude that BBZ compounds are potent antistaphylococcal agents and operate at least in part through DNA gyrase inhibition, leading to the accumulation of single-stranded DNA breaks, and by preventing the binding of gyrase to DNA. [Data is also available from http://bugs.sgul.ac.uk/E-BUGS-106]

2012-10-14 | E-BUGS-106 | biostudies-arrayexpress

DNA supercoiling differences in bacteria result from disparate DNA gyrase activation by polyamines

Project description:DNA supercoiling is essential for all living cells because it controls all processes involving DNA. In bacteria, global DNA supercoiling results from the opposing activities of topoisomerase I, which relaxes DNA, and DNA gyrase, which compacts DNA. These enzymes are widely conserved, sharing >91% amino acid identity between the closely related species Escherichia coli and Salmonella enterica serovar Typhimurium. Why, then, do E. coli and Salmonella exhibit different DNA supercoiling when experiencing the same conditions? We now report that this surprising difference reflects disparate activation of their DNA gyrases by the polyamine spermidine and its precursor putrescine. In vitro, Salmonella DNA gyrase activity was sensitive to changes in putrescine concentration within the physiological range, whereas activity of the E. coli enzyme was not. In vivo, putrescine activated the Salmonella DNA gyrase and spermidine the E. coli enzyme. High extracellular Mg2+ decreased DNA supercoiling exclusively in Salmonella by reducing the putrescine concentration. Our results establish the basis for the differences in global DNA supercoiling between E. coli and Salmonella, define a signal transduction pathway regulating DNA supercoiling, and identify potential targets for antibacterial agents.

2020-10-30 | GSE150757 | GEO

The unusual mode of action of the polyketide glycoside antibiotic cervimycin C [I]

Project description:The resistance to antibiotics is an emerging problem, and necessitates novel antibacterial therapies. Cervimycins A–D are bi-glycosylated polyketides produced by Streptomyces tendae HKI 0179 with promising activity against Gram-positive bacteria. Microscopically, cervimycin C (CmC) treatment caused a spaghetti-like phenotype in Bacillus subtilis 168, with elongated curved cells, which stayed joined after cell division, and exhibited a chromosome segregation defect. Electron microscopy of cervimycin treated S. aureus revealed swelling of some cells, misshaped septa, and cell wall thickening and a rough cell wall surface. Incorporation tests in B. subtilis indicated an effect on DNA metabolism at high cervimycin-concentrations. Indeed, the down-regulation of the DNA gyrase subunit B (gyrB) acted synergistically with cervimycin, and the antibiotic inhibited the in vitro DNA gyrase supercoiling activity. To get a more global view on the mode of action of CmC, transcriptomics and proteomics of cervimycin treated versus untreated S. aureus cells were performed. Interestingly, and in contrast to the previous results, cervimycin did not induce the SOS response in S. aureus, which would indicate disturbance of the DNA gyrase. Instead, cervimycin induced the expression of the CtsR/HrcA heat shock operon and the expression of autolysins. Taken together, we identified the DNA gyrase as one target of cervimycin, but omics data revealed massive alterations in cervimycin treated S. aureus, involving cell wall modifying enzymes and protein stress response, indicating a complex mode of action of cervimycin, that is distinct from other antibiotics.

2024-04-02 | GSE209674 | GEO

Transcription facilitated genome-wide recruitment of topoisomerase I and DNA gyrase

Project description:Genome-wide distribution of topoisomerase I and DNA gyrase is directed by transcription induced supercoiling

2017-01-31 | GSE85357 | GEO

Regulation of gene expression by ArlRS in Staphylococcus aureus USA300 strain LAC

Project description:ArlRS is a two-component regulatory system in Staphylococcus aureus. Here we use RNA-sequencing to compare gene expression in a wild-type USA300 strain and an isogenic arlRS mutant.

2020-04-29 | GSE130887 | GEO

Global gene transcription analysis in response to changes in chromosome supercoiling in Streptomyces coelicolor

Project description:Here, we address the transcriptional response to both novobiocin-induced rapid chromosome relaxation or long-term topological imbalance, both increased and decreased supercoiling, in environmental antibiotic-producing bacteria belonging to the Streptomyces genus.

2019-06-14 | GSE132702 | GEO

Effect of knockout and overexpression of the Streptococcus pneumoniae topoisomerase I regulator StaR on gene expression.

Project description:Strain ∆staRPZnstaR was obtained to investigate genome-wide differential gene expresion when staR gene is reppressed or overexpressed by adding Zn to the culture medium. In addition, gene expression profile alterations produced upon inhibition of gyrase with Novobiocin were studied in the absence and presence of StaR.

2023-04-04 | GSE225261 | GEO

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