グルタチオンは,細胞内病原体のウイルス性遺伝子発現を活性化します
Michelle L Reniere1, Aaron T Whiteley2, Keri L Hamilton3
1Department of Molecular and Cell Biology, University of California, Berkeley, California 94720, USA.
Nature
|January 9, 2015
まとめ
細胞の重要な分子であるグルタチオンは,細胞内病原体Listeria monocytogenesの毒性を活性化します. サプレッサー変異は,この要件を回避し,グルタチオンを明らかにしました.
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.
- パトジェネシス (病原生)
背景:
- 細胞内病原菌は,世界的な疾病負担を大きく引き起こす.
- 宿主細胞内の病原体の生存には,環境感知と毒性の遺伝子調節が必要です.
- Listeria monocytogenesは,哺乳類の細胞に入ると,主ウイルス性調節体であるPrfAを活性化させます.
研究 の 目的:
- Listeria monocytogenesの毒性のレギュレータPrfAを活性化するグルタチオンの役割を調査する.
- グルタチオンがバクテリアの毒性の遺伝子発現と宿主コロニー化に影響を与えるメカニズムを特定する.
主な方法:
- 変異性ウイルス性の細菌変異体を特定するための遺伝子選択.
- マウスモデルでのインビボ減衰試験.
- 抑制変異を特定するためのゲノム配列決定.
- PrfAの活性化メカニズムを解明するための生化学および遺伝的分析.
主要な成果:
- グルタチオン合成に欠けている細菌変異体は,毒性の遺伝子発現が著しく低下し,マウスでは150倍弱体化していた.
- prfAのサプレッサー変異は,グルタチオンとは独立して,構成的に活性なPrfA*タンパク質を生成することによって,毒性を回復させた.
- グルタチオンは直接PrfAにアロステリック結合し,その活性化を媒介する.
結論:
- グルタチオンは,Listeria monocytogenesの毒性のレギュレータPrfAを活性化するために不可欠です.
- グルタチオンは,細胞内病原体の毒性に対する重要なシグナル分子の役割を果たします.
- グルタチオンに依存するPrfAの活性化をターゲットにすることで,リステリア感染症に対する新しい治療戦略を提供することができます.
関連する概念動画
Regulation of Bacterial Virulence
59
Pathogenic bacteria employ a range of regulatory mechanisms to modulate the expression of virulence genes in response to environmental and host-derived signals. These mechanisms ensure that virulence factors are expressed only under favorable conditions, thereby optimizing infection and survival strategies.Mechanisms of Virulence RegulationKey regulatory strategies include:Two-Component Systems: These consist of a membrane-bound sensor kinase and a cytoplasmic response regulator. Environmental...
59
Gene Regulation in Microbial Communities: Quorum Sensing
926
Quorum sensing is a mechanism of bacterial communication that enables coordinated gene expression in response to changes in population density. This facilitates collective behaviors that enhance survival, resource acquisition, and ecological adaptation. This process relies on small signaling molecules called autoinducers that accumulate as bacterial populations grow. When a critical threshold concentration of autoinducers is reached, bacterial cells collectively modify gene expression,...
926
Colonisation of Pathogens
64
Pathogen colonization of host tissues is a critical step in the development of infectious diseases. Various pathogenic microorganisms, including bacteria, fungi, viruses, and protozoa, have evolved complex strategies to attach to, invade, and persist within host environments. These mechanisms enable pathogens to establish infections, evade immune responses, and resist antimicrobial treatments.Attachment to Host CellsIn bacteria, colonization typically begins with adherence to host epithelial...
64
Bacterial Toxins
108
Bacterial toxins are sophisticated virulence factors that enable pathogenic bacteria to interact with, invade, and damage host tissues. These toxins fall broadly into two types: protein exotoxins, which are secreted into the environment and target specific host receptors, and lipopolysaccharide endotoxins, which are structural components of the bacterial outer membrane released primarily during bacterial lysis or membrane shedding. Exotoxins generally act more selectively, binding to cell...
108
Immune Response Against Viral Pathogens
2.7K
The immune system's response to viral infections is a complex and coordinated process involving natural killer (NK) cells, T cell-mediated responses, and antibody-mediated responses.
NK Cells
NK cells are a crucial part of our innate immune system, acting as the first line of defense against viral infections. These cells can recognize and kill infected cells without prior exposure to the virus, effectively slowing down the spread of infection. Additionally, NK cells produce proinflammatory...
NK Cells
NK cells are a crucial part of our innate immune system, acting as the first line of defense against viral infections. These cells can recognize and kill infected cells without prior exposure to the virus, effectively slowing down the spread of infection. Additionally, NK cells produce proinflammatory...
2.7K
Bacterial Translocation and Protein Secretion
1.1K
Bacterial protein secretion involves translocation systems to ensure proteins reach their designated locations, including the plasma membrane, periplasm, outer membrane, or the external environment. These translocation systems are vital for bacterial physiology, supporting processes like membrane assembly, enzymatic activity in the periplasm, and interactions with the external environment. The division of labor between Sec and Tat pathways ensures efficiency in handling proteins with diverse...
1.1K


