分泌される転写因子は,Mycobacterium tuberculosisの毒性を制御する
Sridharan Raghavan1, Paolo Manzanillo, Kaman Chan
1Department of Microbiology and Immunology, Program in Microbial Pathogenesis and Host Defense, University of California, San Francisco, 600 16th Street, Campus Box 2200, San Francisco, California 94143-2200, USA.
Nature
|August 8, 2008
まとめ
新しく発見されたレギュレータであるEspRは,Mycobacterium tuberculosisのESX-1分泌システムを制御しています. このシステムは結核の毒性にとって不可欠であり,EspRの分泌を含む負のフィードバックループによって調節されます.
科学分野:
- 微生物学 微生物学とは
- 分子生物学は分子生物学である.
- 免疫学 免疫学とは
背景:
- Mycobacterium tuberculosisは,宿主細胞に毒性の要因を供給するために特殊な分泌システムを利用しています.
- ESX-1分泌システムは,M. tuberculosisの毒性にとって極めて重要ですが,その調節は依然として十分に理解されていません.
研究 の 目的:
- M. tuberculosisにおけるESX-1分泌システムの主要レギュレータを特定し,特徴づけること.
- ESX-1システムの規制メカニズムを解明する.
主な方法:
- ESX-1の調節とM. tuberculosisの毒性におけるEspR (Rv3849) の役割を調査した.
- EspRによるRv3616c-Rv3614cオペロンの転写活性化を分析した.
- ESX-1システムによるEspRの分泌とその遺伝子発現への影響について調べました.
主要な成果:
- EspRは,マウスモデルにおけるESX-1分泌とM. tuberculosisの毒性にとって不可欠である.
- EspRは,Rv3616c-Rv3614cオペロンのプロモーターを直接結合して活性化する.
- EspRはESX-1システムによって分泌され,ESX-1の活動を減少させる負のフィードバックループを作成します.
結論:
- EspRは,ESX-1分泌システムの重要な調節剤として作用します.
- 新しいネガティブなフィードバックメカニズムは,EspR分泌を通してESX-1の活動を制御します.
- ESX-1分泌の微調整は,分泌される因子の抗原性により,M. tuberculosisの病原化に不可欠である可能性が高い.
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