グラン酵素Bは細菌の中央代謝とタンパク質合成を妨害し,免疫細胞死亡プログラムを促進する
Farokh Dotiwala1, Sumit Sen Santara2, Andres Ariel Binker-Cosen3
1Program in Cellular and Molecular Medicine, Boston Children's Hospital, Boston, MA 02115, USA; Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA; Vaccine Center, Wistar Institute, Philadelphia, PA 19104, USA.
Cell
|November 7, 2017
まとめ
ヒトの細胞毒性リンパ球は,必要不可欠なタンパク質を標的として,バクテリアを殺すために,グラン酵素Bを使用します. この多角的な攻撃は 生命の重要な経路を妨害し 細菌の抵抗を不可能にします
科学分野:
- 免疫学
- 微生物学
- プロテオミクス
背景:
- 人間の細胞毒性リンパ球は,グラン酵素タンパク質を含む細胞毒性粒子を用いて細胞内微生物を排除する.
- グラン酵素プロテアゼは,電子輸送を妨害し,防御機能を無効化することによって,酸化的ダメージを通して細菌の死を誘発しますが,無酸素細菌の非酸化的死も引き起こします.
研究 の 目的:
- 微分プロテオミクスを用いて,3つの異なる細菌種でグラン酵素B基底を特定する.
- 細菌におけるグラン酵素Bの保存標的と宿主防御への影響を理解する.
主な方法:
- 差分プロテオミクスを用いて,グラン酵素B基底を分析した.
- この研究は,エシェリキア・コライ,リステリア・モノサイトゲネス,およびミコバクテリア・結核という3つの関連のない細菌に焦点を当てた.
主要な成果:
- グラン酵素Bは様々な種の細菌の生存に不可欠な 保存されたタンパク質を分割します
- 特定された主要な基質には,重要な生物合成と代謝経路に関与するタンパク質が含まれています.
- タンパク質合成,折り畳み,分解に不可欠なタンパク質,例えばアミノアシルtRNA合成酵素,リボソームタンパク質,チャペロン,Clp系を標的とする.
結論:
- Granzyme Bは多岐にわたる戦略を採用し 細菌の保存された重要な経路をターゲットにしています
- 細菌の重要な機能の広範なターゲティングは,細胞毒性リンパ球攻撃に対する耐性を培うことがバクテリアにとって困難であることを示唆する.
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