論文 - 詳細
| RRC ID | 50608 |
|---|---|
| 著者 | Morales EH, Pinto CA, Luraschi R, Muñoz-Villagrán CM, Cornejo FA, Simpkins SW, Nelson J, Arenas FA, Piotrowski JS, Myers CL, Mori H, Vásquez CC. |
| タイトル | Accumulation of heme biosynthetic intermediates contributes to the antibacterial action of the metalloid tellurite. |
| ジャーナル | Nat Commun |
| Abstract |
The metalloid tellurite is highly toxic to microorganisms. Several mechanisms of action have been proposed, including thiol depletion and generation of hydrogen peroxide and superoxide, but none of them can fully explain its toxicity. Here we use a combination of directed evolution and chemical and biochemical approaches to demonstrate that tellurite inhibits heme biosynthesis, leading to the accumulation of intermediates of this pathway and hydroxyl radical. Unexpectedly, the development of tellurite resistance is accompanied by increased susceptibility to hydrogen peroxide. Furthermore, we show that the heme precursor 5-aminolevulinic acid, which is used as an antimicrobial agent in photodynamic therapy, potentiates tellurite toxicity. Our results define a mechanism of tellurite toxicity and warrant further research on the potential use of the combination of tellurite and 5-aminolevulinic acid in antimicrobial therapy. |
| 巻・号 | 8 |
| ページ | 15320 |
| 公開日 | 2017-5-11 |
| DOI | 10.1038/ncomms15320 |
| PII | ncomms15320 |
| PMID | 28492282 |
| PMC | PMC5437285 |
| MeSH | Aminolevulinic Acid / pharmacology Anti-Bacterial Agents / pharmacology* Biosynthetic Pathways* / drug effects Drug Resistance, Bacterial / drug effects Escherichia coli / drug effects Escherichia coli / genetics Escherichia coli / metabolism Genome, Bacterial Heme / biosynthesis* Iron Deficiencies Metalloids / pharmacology* Microbial Sensitivity Tests Models, Biological Mutation / genetics Protoporphyrins / pharmacology Superoxides / metabolism Tellurium / pharmacology* Tellurium / toxicity |
| IF | 12.121 |
| 引用数 | 9 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
|
| 最多言及媒体 | Patent(IFI CLAIMS) |
| 各媒体での言及数の合計 | 7 |
| 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) | BW25113 JW3838-KC JW2429-KC |