論文 - 詳細
| RRC ID | 3943 |
|---|---|
| 著者 | Dwyer DJ, Kohanski MA, Hayete B, Collins JJ. |
| タイトル | Gyrase inhibitors induce an oxidative damage cellular death pathway in Escherichia coli. |
| ジャーナル | Mol Syst Biol |
| Abstract |
Modulation of bacterial chromosomal supercoiling is a function of DNA gyrase-catalyzed strand breakage and rejoining. This reaction is exploited by both antibiotic and proteic gyrase inhibitors, which trap the gyrase molecule at the DNA cleavage stage. Owing to this interaction, double-stranded DNA breaks are introduced and replication machinery is arrested at blocked replication forks. This immediately results in bacteriostasis and ultimately induces cell death. Here we demonstrate, through a series of phenotypic and gene expression analyses, that superoxide and hydroxyl radical oxidative species are generated following gyrase poisoning and play an important role in cell killing by gyrase inhibitors. We show that superoxide-mediated oxidation of iron-sulfur clusters promotes a breakdown of iron regulatory dynamics; in turn, iron misregulation drives the generation of highly destructive hydroxyl radicals via the Fenton reaction. Importantly, our data reveal that blockage of hydroxyl radical formation increases the survival of gyrase-poisoned cells. Together, this series of biochemical reactions appears to compose a maladaptive response, that serves to amplify the primary effect of gyrase inhibition by oxidatively damaging DNA, proteins and lipids. |
| 巻・号 | 3 |
| ページ | 91 |
| 公開日 | 2007-1-1 |
| DOI | 10.1038/msb4100135 |
| PII | msb4100135 |
| PMID | 17353933 |
| PMC | PMC1847949 |
| MeSH | Adenosine Triphosphate / metabolism Enzyme Inhibitors / pharmacology* Escherichia coli / cytology Escherichia coli / drug effects* Escherichia coli / metabolism Gene Expression Hydroxyl Radical / metabolism Iron / metabolism Oxidative Stress* Topoisomerase II Inhibitors* |
| IF | 8.991 |
| 引用数 | 270 |
| WOS 分野 | BIOCHEMISTRY & MOLECULAR BIOLOGY |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | Patent(IFI CLAIMS) |
| 各媒体での言及数の合計 | 9 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| 原核生物(大腸菌) | ME9062 (BW25113 ) |