炎症性腸疾患における生物活性微生物遺伝子産物の発見
Yancong Zhang1,2,3, Amrisha Bhosle1,2,3, Sena Bae2,3,4
1Infectious Disease and Microbiome Program, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Nature
|May 25, 2022
まとめ
研究者らは,炎症性腸疾患 (IBD) と関連している可能性のある 340,000 以上の微生物タンパク質ファミリーを特定しました. この発見は,微生物群の理解を広げる
科学分野:
- 微生物群の研究
- 免疫学
- バイオ情報学
背景:
- 微生物群とその生物活性化合物は炎症性腸疾患 (IBD) で破壊される.
- 微生物のタンパク質の重要な部分は,特に腸内では,特徴づけられていませんが,潜在的に生物活性です.
研究 の 目的:
- IBDにおける腸内炎症に関連した潜在的に生物活性な微生物タンパク質の家族を体系的に特定する.
- IBD に関する,これまで記述されていない微生物のタンパク質を機能的に特徴づける.
主な方法:
- メタゲノミクス,メタトランスクリプトミクス,メタプロテオミクスを組み合わせて,生物活性微生物のタンパク質を特定し,優先順位付けした.
- マイクロバイオームにおける新しい生物活性元素を特定するためのMetaWIBELEワークフローを開発し,使用しました.
- 免疫性およびバイオフィルム形成の評価を含む標的型実験による検証された予測.
主要な成果:
- IBD の文脈で 340,000 以上の潜在的に生物活性なタンパク質ファミリーが特定され,約半分は以前に特徴づけられていなかった.
- 粘着因子やフォン・ウィレブランド型因子などの宿主-微生物の相互作用に関与する特定のタンパク質の生物活性に関する証拠を提供した.
- Enterobacteriaceae pilinsの差異的免疫性を示し,バクテロイドのバイオフィルム形成におけるフォン・ウィレブランド因子ホモログの役割を特定した.
結論:
- MetaWIBELEの方法論は,多様なコミュニティとフェノタイプで新しい生物活性元素を発見するための汎用的なアプローチです.
- IBDでは数千の候補微生物タンパク質が 宿主免疫システムと相互作用し 治療対象となる可能性があります
- この研究は慢性疾患における生物活性遺伝子産物の理解を拡大し,治療開発のための要約を提供します.
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