AirSRは [2Fe-2S] クラスターを含む2つのコンポーネントのシステムで,Staphylococcus aureusでグローバルな酸素感知と酸化還元信号を媒介する
Fei Sun1, Quanjiang Ji, Marcus B Jones
1Department of Chemistry and Institute for Biophysical Dynamics, The University of Chicago, Chicago, Illinois 60637, USA.
Journal of the American Chemical Society
|November 30, 2011
まとめ
Staphylococcus aureusは,AirSRシステムを用いて,酸化信号を酸化還元活性鉄硫黄集束を通して感知する. このシステムは何百もの遺伝子を調節し,酸素が限られた条件下で抗生物質耐性を影響する.
科学分野:
- 微生物学 微生物学とは
- バクテリアの生理学
- レドックスシグナリング
背景:
- 酸素感知とリドックスシグナル伝達は,細菌の生理学と宿主-病原体相互作用にとって重要である.
- 2つのコンポーネントのシステムは,バクテリアの重要なレギュレータであり,しばしば環境のシグナルに反応します.
研究 の 目的:
- 酸化信号に反応するStaphylococcus aureus AirSRの2つの成分システムの機能とメカニズムを解明する.
- AirSキナーゼ活性における鉄硫黄クラスタの役割と,遺伝子調節と抗生物質耐性に対するその影響について調査する.
主な方法:
- [2Fe-2S]クラスタの役割を研究するためのサイト指向型変異.
- [2Fe-2S]クラスタのインビトロ再構成.システイン脱硫酵素の同種を用いた.
- リン酸化測定は,キナーゼ活性を決定する.
- トランスクリプトーム分析 (RNA-seq) で,調節された遺伝子を特定する.
- 抗菌剤耐性アッセイ 抗菌剤耐性アッセイ 抗菌剤耐性アッセイ
主要な成果:
- AirS内の [2Fe-2S] クラスターは,そのキナーゼ活性に不可欠であり,酸化された [2Fe-2S] 2+) 形態が完全に活性化されています.
- クラスタの過酸化または還元により,AirS.が無効になります.
- airRの変異は,無酸素状態で約355の遺伝子の発現に影響します.
- airR変異体は,無酸素状態でH2O2,バンコミシン,ノルフロクサシン,シプロフロクサシンに対する耐性が高まっている.
結論:
- Staphylococcus aureus AirSRは,レドックス依存の世界的な規制システムである.
- このシステムは,AirS内のリドックス活性鉄硫黄クラスタを使用して,酸化信号を感知します.
- AirSRは,遺伝子調節において重要な役割を果たし,酸素の限られた条件下で,様々な薬剤に対する耐性を授与します.
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