哈尔科福尔介导的呼吸氧化酶控制灵活性M. 结核病的毒性 结核病的毒性
John A Buglino1, Yaprak Ozakman1, Chad E Hatch2
1Immunology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, New York 10065 USA.
结核病细菌使用特殊的分子称为 chalkophores 捕获铜,这是他们能源生产的必要条件. 这有助于它们在宿主体内通过维持呼吸而生存,尽管免疫防御.
科学领域:
- 微生物学 微生物学
- 分子生物学分子生物学
- 免疫学 免疫学 免疫学
背景情况:
- 结核病 (TB) 是一个主要的全球健康威胁,由*Mycobacterium tuberculosis* (Mtb) 引起.
- Mtb的能量生产途径,氧化酸化,是关键的治疗标.
- 在宿主感染期间,Mtb如何维持呼吸仍然不清楚.
研究的目的:
- 为了研究Mtb合成的合体在感染期间获得铜和呼吸中的作用.
- 为了确定 chalkophores 在宿主-病原体相互作用和 Mtb 生存中的功能.
主要方法:
- 缺少藻生物合成的Mtb突变体的遗传分析.
- 在有限的铜条件下评估Mtb呼吸,ATP生产和生存率.
- 在体内研究使用小鼠模型来评估Mtb衰减.
主要成果:
- 在铜限量下,mtb合体对于维持血铜呼吸超复合体至关重要.
- 甲基缺陷严重损害了Mtb的生存,呼吸和ATP的产生,特别是当细胞染色体BD氧化酶也缺少时.
- 在小鼠中,缺乏合体的mtb被减弱,这种表型因失去了cytochrome BD氧化酶而恶化.
- 宿主免疫压力对甲基缺乏的Mtb是独立于适应性免疫和中性粒细胞的.
结论:
- Mtb chalkophores抵消宿主诱导的铜剥夺,确保呼吸功能.
- 一个多层次的系统,涉及体和呼吸氧化酶,使Mtb能够在感染期间保持呼吸.
- 准石灰介导的铜获取是一种潜在的治疗策略来对抗结核病.
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