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バクテリオファージは,バクテリアのcGASのような免疫機能を抑制し,回避する

Erin Huiting¹, Xueli Cao², Jie Ren³

¹Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA 94158, USA.

|February 7, 2023

まとめ

細菌は,ファグと戦うサイクルGMP-AMP合成酵素 (cGAS) ベースの免疫システム (CBASS) を備えている. ファージは抗CBASSタンパク質でこの防御に抵抗し進化の軍拡競争を引き起こします

科学分野:

微生物学
免疫学
分子生物学

背景:

ユカリオットの抗ウイルス免疫はcGAS-STING経路に依存し,2',3'-cGAMPを合成する.
CBASSとして知られるバクテリアのサイクルGMP- AMP合成酵素 (cGAS) のような酵素は,抗ファージ活性のためのサイクルオリゴヌクレオチドを生成するが,内生的な機能は証明されていない.

研究の目的:

Pseudomonas aeruginosaにおけるCBASSの内生抗菌活性について調査する.
バクテリアの抗菌体防御と抗菌体防御の仕組みを理解する.

主な方法:

Pseudomonas aeruginosaの内生的なcGASのような酵素の特定
病原菌感染時の周期性核酸合成 (3',3'-cGAMP) の分析
抗CBASSタンパク質 (Acb2) と周期性核酸およびエフェクタとの相互作用の特徴
遺伝子変異によるファグ逃避戦略の評価

主要な成果:

P. aeruginosaの内生的なcGASのような酵素は,ファグの感染時に3',3'-cGAMPを生成し,ファグの複製を制限するフォスフォリパースエフェクターを活性化します.
ファージは,哺乳類のcGAS製品を含む3',3'-cGAMPおよび他の周期性ヌクレオチドを結合することによって,フォスフォリファースの活性を抑制する抗CBASSタンパク質であるAcb2を進化させた.
CBASSはファグの複製とリソゲン誘導を効果的に阻害しますが,ファグは主要なカプシド遺伝子の変異によってこの防御を回避することができます.

結論:

この研究では,細菌におけるCBASSの内生抗菌機能が示されています.
CBASSは洗練された抑制と回避戦略を採用し,バクテリアとファグのダイナミックな共進化関係を強調しています.
この発見は,種間でのcGASベースの免疫に対するAcb2の広範な抑制可能性を明らかにしています.

キーワード:

CBASS についてプセドモナス・エアルギノサ acb についてアンチCBASS アンチファージ免疫バクテリオファージ cGAS についてカプシドエスケーパー生まれつきの免疫

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