Iron chelation increases the tolerance of Escherichia coli to hyper-replication stress
| Autor: | Charlotte Dahlmann Liboriussen, Peter W. Thulstrup, Rasmus N. Klitgaard, Godefroid Charbon, Sonia I. Maffioli, Stefano Donadio, Anders Løbner-Olesen |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
DNA Replication
DNA Bacterial 0301 basic medicine lcsh:Medicine Deferoxamine Iron Chelating Agents medicine.disease_cause Article 03 medical and health sciences chemistry.chemical_compound Bacterial Proteins Escherichia coli medicine Topoisomerase II Inhibitors lcsh:Science chemistry.chemical_classification Reactive oxygen species Multidisciplinary lcsh:R DNA replication Processivity Chromosomes Bacterial DnaA DNA-Binding Proteins Oxidative Stress 030104 developmental biology chemistry Biochemistry Replication Initiation lcsh:Q Reactive Oxygen Species DNA medicine.drug |
| Zdroj: | Scientific Reports Scientific Reports, Vol 8, Iss 1, Pp 1-14 (2018) Charbon, G, Klitgaard, R N, Liboriussen, C D, Thulstrup, P W, Maffioli, S I, Donadio, S & Løbner-Olesen, A 2018, ' Iron chelation increases the tolerance of Escherichia coli to hyper-replication stress ', Scientific Reports, vol. 8, no. 1, 10550 . https://doi.org/10.1038/s41598-018-28841-9 |
| ISSN: | 2045-2322 |
| DOI: | 10.1038/s41598-018-28841-9 |
| Popis: | In Escherichia coli, an increase in the frequency of chromosome replication is lethal. In order to identify compounds that affect chromosome replication, we screened for molecules capable of restoring the viability of hyper-replicating cells. We made use of two E. coli strains that over-initiate DNA replication by keeping the DnaA initiator protein in its active ATP bound state. While viable under anaerobic growth or when grown on poor media, these strains become inviable when grown in rich media. Extracts from actinomycetes strains were screened, leading to the identification of deferoxamine (DFO) as the active compound in one of them. We show that DFO does not affect chromosomal replication initiation and suggest that it was identified due to its ability to chelate cellular iron. This limits the formation of reactive oxygen species, reduce oxidative DNA damage and promote processivity of DNA replication. We argue that the benzazepine derivate (±)-6-Chloro-PB hydrobromide acts in a similar manner. |
| Databáze: | OpenAIRE |
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