タイプIIIの分泌システムエフェクターは,堅牢で柔軟な細胞内毒性ネットワークを形成する
David Ruano-Gallego1, Julia Sanchez-Garrido1, Zuzanna Kozik2
1Centre for Molecular Microbiology and Infection, Department of Life Sciences, Imperial College, London, UK.
まとめ
グラム陰性病原体におけるタイプIII分泌システム (T3SS) エフェクタネットワークは,病原性を維持しながら,著しい遺伝子損失を許容し,非常に強固である. このネットワークは
科学分野:
- 微生物学
- 分子生物学
- 免疫学
背景:
- グラム陰性細菌の感染は,しばしばIII型分泌システム (T3SS) エフェクターを使用して宿主細胞を操作する.
- これらのエフェクターは病原体の毒性や宿主の免疫回避に不可欠です.
研究 の 目的:
- グラム陰性病原体におけるT3SSエフェクターネットワークの強度と適応性を調査する.
- エフェクタネットワークの収縮が病原性および宿主免疫反応に与える影響を決定する.
主な方法:
- Citrobacter rodentiumをモデル生物として利用し,その31のT3SSエフェクタの配列的な遺伝子削除を行った.
- 病原性および免疫反応を評価するためにマウスにおける感染モデルを*in vivo*で使用した.
- 機械学習モデルを開発し 100以上のミュータントの組み合わせで コロニー化結果を予測しました
主要な成果:
- T3SSエフェクタネットワークは,病原性を維持しながら,最大60%の収縮を許容し,著しい強度を示した.
- 異なるエフェクタネットワークは,異なる宿主サイトカインプロファイル (例えば,IL-22,IL-17,IFN-γ,GM-CSF) を誘発したが,すべて保護免疫を誘発した.
- 機械学習モデルは コロニー化結果を正確に予測し 実験的に検証しました
- 人間限定のエフェクターレパートリーを移転することは,エフェクターネットワークの宿主適応の役割を示唆する"C. rodentium"に効率的なコロニー化をもたらさなかった.
結論:
- T3SSエフェクターネットワークは,宿主感染時の適応性を強調して,遺伝的変異に対する顕著な回復力を発揮します.
- ホストの免疫反応は堅固で,多様なT3SSエフェクタネットワーク組成に適応できます.
- エフェクタネットワークの構成は,病原体の宿主適応と宿主範囲において重要な役割を果たします.
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