アミノグリコシド抗生物質は,細菌のバイオフィルム形成を誘発する
Lucas R Hoffman1, David A D'Argenio, Michael J MacCoss
1Department of Pediatrics, University of Washington, Seattle, Washington 98195, USA.
Nature
|August 27, 2005
まとめ
亜致死性アミノグリコシド抗生物質は,Pseudomonas aeruginosaのようなバクテリアのバイオフィルム形成を誘発する. 新しく特定された遺伝子であるアミノグリコシド応答調節体 (arr) は,このプロセスに不可欠であり,抗生物質耐性を高めます.
科学分野:
- 微生物学 微生物学とは
- バクテリア病原菌の発生
- 薬剤耐性 薬剤耐性 薬剤耐性 薬剤耐性 薬剤耐性 薬剤耐性 薬剤耐性
背景:
- バクテリアのバイオフィルムは,抗生物質治療に抵抗し,慢性感染症に寄与する持続的なコミュニティです.
- バイオフィルム形成メカニズムの理解は,システィック線維症患者のPseudomonas aeruginosaなどの持続的な細菌感染症の治療に不可欠です.
研究 の 目的:
- アミノグリコシド抗生物質の亜抑制濃度が,細菌のバイオフィルム形成にどのように影響するかを調査する.
- 抗生物質誘発バイオフィルム形成に関与する遺伝的要因と分子経路を特定する.
主な方法:
- Pseudomonas aeruginosaとEscherichia coliの亜抑制性アミノグリコシド濃度への暴露.
- P. aeruginosa.における特定された"アミノグリコシド応答調節体" (arr) 遺伝子の遺伝子解析.
- バクテリア膜におけるサイクルディグアナシンモノフォスファート (c-di-GMP) フォスフォディエステラーゼの活性度の測定.
- トブラミシンに対する反応におけるバイオフィルム形成とGTPによる抑制の評価.
主要な成果:
- 亜抑制性アミノグリコシド抗生物質は,P. aeruginosaとE. coliのバイオフィルム形成を誘導する.
- "アミノグリコシド応答調節体" (arr) 遺伝子は,この誘導に不可欠であり,バイオフィルム固有の耐性を授与する.
- Arrはc-di-GMPフォスフォディエステラーゼをコードし,arr変異体はフォスフォディエステラーゼの活性が低下しています.
- トブラミシン誘発のバイオフィルム形成は,c-di-GMPレベルの変化によって媒介されます.
結論:
- バクテリアのバイオフィルム形成は,抗生物質の存在に対する防御反応である可能性があります.
- アール遺伝子とサイクルジグアナシンモノフォスファート (c-di-GMP) レベルの調節は,この抗生物質誘発バイオフィルム形成の鍵です.
- この発見は,慢性細菌感染症との闘いに新たな標的を提示する可能性がある.
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