RNAi依存のエピミュテーションによって引き起こされる抗真菌薬剤耐性
Silvia Calo1, Cecelia Shertz-Wall1, Soo Chan Lee1
1Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, North Carolina 27710, USA.
Nature
|August 1, 2014
まとめ
Mucor circinelloidesは,安定したメンデルの変異または不安定な表遺伝子RNA干渉 (RNAi) 媒介によるfkbA遺伝子の静止により,抗真菌薬耐性を発達させる.
科学分野:
- ミコロジー菌類学
- 分子生物学は分子生物学である.
- 遺伝学 遺伝学とは
背景:
- 微生物は様々な適応メカニズムを進化させています.
- 抗真菌薬剤耐性は,公衆衛生上の懸念が高まっています.
- ヒトの真菌病原体Mucor circinelloidesの適応メカニズムは完全に理解されていません.
研究 の 目的:
- 抗真菌薬FK506 (タクロリムス) に対する自発的な耐性のメカニズムをMucor circinelloidesで調査する.
- 薬剤耐性におけるメンデルの変異と表遺伝経路の役割を明らかにする.
- 新しいRNA干渉 (RNAi) ベースのエピミュテーションメカニズムの発見.
主な方法:
- fkbA,cnbR,およびcnaA遺伝子の突然変異の遺伝子解析. fkbA,cnbR,およびcnaA遺伝子の突然変異の遺伝子解析. fkbA,cnbR,およびcnaA遺伝子の突然変異の遺伝子解析. fkbA,cnbR,およびcnaA遺伝子の突然変異の遺伝子解析.
- FK506の抵抗性とハイファの成長の評価.
- RNA干渉 (RNAi) 経路分析.RNA干渉 (RNAi) 経路分析.RNA干渉 (RNAi) 経路分析.RNA干渉 (RNAi) 経路分析.RNA干渉 (RNAi) 経路分析.RNA干渉 (RNAi) 経路分析.RNA干渉 (RNAi) 経路分析.RNA干渉 (RNAi) 経路分析.RNA干渉 (RNAi) 経路分析.
- fkbA小RNAの検出とアンチセンセスのRNA生成.
主要な成果:
- FK506耐性の2つの異なるメカニズムが特定されました:安定したメンデルの変異と,fkbA.の不安定なRNAi媒介の表遺伝子シューリング.
- RNAi媒介による静止は,薬剤耐性エピムタンスを生み出し,容易に敏感なフェノタイプに戻ります.
- サイレンシングは,二重鎖のRNAトリガーの生成を含み,RNAi経路を必要とします.
- FK506耐性エピムタンスは,豊富なfkbA小RNAと関連しています.
結論:
- Mucor circinelloidesは,フェノタイプ性可塑性および薬剤耐性のための新しいエピジェネティックRNAiベースのエピミュテーションメカニズムを使用しています.
- このメカニズムは,迅速な,しかし不安定な適応戦略を提供します.
- この発見は,抗微生物薬剤耐性およびeukaryotesのRNAi調節を理解するための意味を持っています.
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