使用机器学习来剖析Leishmania内部化和发展所需的宿主激酶
Ling Wei1, Umaru Barrie2, Gina M Aloisio2
1Center for Global Infectious Disease Research, Seattle Children's Research Institute, Seattle, WA 98109, United States.
Molecular and biochemical parasitology
|August 24, 2024
概括
研究人员确定了调节Leishmania寄生虫吸收和巨细胞生存的宿主激酶. 这项研究揭示了新的激酶,并强调了在感染期间参与宿主-病原体相互作用的复杂激酶网络.
科学领域:
- 宿主-病原体相互作用
- 细胞生物学 细胞生物学
- 免疫学 免疫学 免疫学
背景情况:
- 莱什曼尼亚寄生虫感染哺乳动物,在和宿主细胞之间循环.
- 细胞吸收寄生虫和巨细胞内的生存对于疾病的建立至关重要.
- 主体激酶在调节这些过程中发挥着作用.
研究的目的:
- 为了识别Leishmania的宿主激酶调节者,巨细胞通过前性和前性细胞的吸收.
- 为了发现寄生虫在宿主细胞内生存的酶.
- 为了区分寄生虫特定的吸收机制与一般的细胞化.
主要方法:
- 一个基于图像的酶回归屏幕,使用38种酶抑制剂.
- 以补充剂/C3bi或IgG为控制器涂层的向惰性珠子.
- 分析受体介导的细胞和寄生虫内部化中的酶作用.
主要成果:
- 识别了已知的激酶 (Src家族激酶,Abl家族激酶,SYK) 和新型激酶,调节了Leishmania吸收.
- 预测宿主激酶对于前虫转化为前虫和前虫存活至关重要.
- 发现酶优先调节寄生虫吸收,而不是珠子吸收.
结论:
- 需要多个相互连接的宿主激酶网络来感染Leishmania.
- 参与寄生虫生命周期阶段的激酶可以根据受体结合和生命周期阶段而有所不同.
- 莱什曼尼亚内部化的宿主激酶调节可能涉及与一般化细胞化不同的机制.
相关概念视频
Leishmaniasis
Leishmaniasis is a protozoal disease caused by species of the genus Leishmania and transmitted through the bite of infected female sandflies. The parasite exists in two principal morphological forms during its life cycle. A sandfly acquires intracellular amastigotes from an infected reservoir host, such as a dog. Within the sandfly, these forms differentiate into motile, flagellated promastigotes. During a subsequent blood meal, promastigotes are injected into the human host, where they...
Antiprotozoal Agents
Leishmaniasis is a widespread parasitic disease caused by several Leishmania species. It affects millions of people each year and remains a major public health problem in endemic regions. First-line treatment relies on pentavalent antimonials, including meglumine antimoniate and sodium stibogluconate. Even so, how these drugs work has not been fully clear, especially their interaction with parasite-specific biochemical pathways. One key target is trypanothione reductase (TR), an enzyme that...


