論文 - 詳細
| RRC ID | 53700 |
|---|---|
| 著者 | Robinson JL, Brynildsen MP. |
| タイトル | An ensemble-guided approach identifies ClpP as a major regulator of transcript levels in nitric oxide-stressed Escherichia coli. |
| ジャーナル | Metab Eng |
| Abstract |
The importance of NO(∙) to immunity is highlighted by the diversity of pathogens that require NO(∙)-defensive systems to establish infections. Proteases have been identified to aid pathogens in surviving macrophage attack, inspiring us to investigate their role during NO(∙) stress in Escherichia coli. We discovered that the elimination of ClpP largely impaired NO(∙) detoxification by E. coli. Using a quantitative model of NO(∙) stress, we employed an ensemble-guided approach to identify the underlying mechanism. Iterations of in silico analyses and corresponding experiments identified the defect to result from deficient transcript levels of hmp, which encodes NO(∙) dioxygenase. Interestingly, the defect was not confined to hmp, as ΔclpP imparted widespread perturbations to the expression of NO(∙)-responsive genes. This work identified a target for anti-infective therapies based on disabling NO(∙) defenses, and demonstrated the utility of model-based approaches for exploring the complex, systems-level stress exerted by NO(∙). |
| 巻・号 | 31 |
| ページ | 22-34 |
| 公開日 | 2015-9-1 |
| DOI | 10.1016/j.ymben.2015.06.005 |
| PII | S1096-7176(15)00073-7 |
| PMID | 26112956 |
| MeSH | Biocatalysis Dihydropteridine Reductase / genetics* Endopeptidase Clp / physiology* Escherichia coli / genetics* Escherichia coli / metabolism Escherichia coli Proteins / genetics* Escherichia coli Proteins / physiology* Hemeproteins / genetics* NADH, NADPH Oxidoreductases / genetics* Nitric Oxide / metabolism* Promoter Regions, Genetic RNA, Messenger / analysis* Sequence Analysis, RNA Stress, Physiological Transcription, Genetic |
| IF | 7.263 |
| 引用数 | 15 |
| 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 | 3 |
| 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) | |