論文 - 詳細
| RRC ID | 35564 |
|---|---|
| 著者 | Amato SM, Orman MA, Brynildsen MP. |
| タイトル | Metabolic control of persister formation in Escherichia coli. |
| ジャーナル | Mol Cell |
| Abstract |
Bacterial persisters are phenotypic variants that form from the action of stress response pathways triggering toxin-mediated antibiotic tolerance. Although persisters form during normal growth from native stresses, the pathways responsible for this phenomenon remain elusive. Here we have discovered that carbon source transitions stimulate the formation of fluoroquinolone persisters in Escherichia coli. Further, through a combination of genetic, biochemical, and flow cytometric assays in conjunction with a mathematical model, we have reconstructed a molecular-level persister formation pathway from initial stress (glucose exhaustion) to the activation of a metabolic toxin-antitoxin (TA) module (the ppGpp biochemical network) resulting in inhibition of DNA gyrase activity, the primary target of fluoroquinolones. This pathway spans from initial stress to antibiotic target and demonstrates that TA behavior can be exhibited by a metabolite-enzyme interaction (ppGpp-SpoT), in contrast to classical TA systems that involve only protein and/or RNA. |
| 巻・号 | 50(4) |
| ページ | 475-87 |
| 公開日 | 2013-5-23 |
| DOI | 10.1016/j.molcel.2013.04.002 |
| PII | S1097-2765(13)00283-9 |
| PMID | 23665232 |
| MeSH | Adaptation, Physiological / drug effects* Adaptation, Physiological / genetics Ampicillin / pharmacology Anti-Bacterial Agents / pharmacology* Antitoxins / genetics Antitoxins / metabolism Bacterial Load Bacterial Toxins / genetics Bacterial Toxins / metabolism Carbon / metabolism* Cyclic AMP / pharmacology Escherichia coli / genetics Escherichia coli / metabolism* Escherichia coli Proteins / genetics Escherichia coli Proteins / metabolism Fluoroquinolones / pharmacology Glucose / metabolism Guanosine Tetraphosphate / metabolism Microbial Viability / drug effects Microbial Viability / genetics Ofloxacin / pharmacology Pyrophosphatases / genetics Pyrophosphatases / metabolism Signal Transduction / drug effects Signal Transduction / genetics Time Factors |
| IF | 15.584 |
| 引用数 | 179 |
| WOS 分野 | BIOCHEMISTRY & MOLECULAR BIOLOGY CELL BIOLOGY |
| リソース情報 | |
| 原核生物(大腸菌) | Keio collection pBAD33? |