使用机器学习来剖析用于Leishmania内部化和发展所需的宿主激酶
Ling Wei1, Umaru Barrie2,3, Gina M Aloisio2,3
1Center for Global Infectious Disease Research, Seattle Children's Research Institute, Seattle, WA 98109, United States.
bioRxiv : the preprint server for biology
|May 27, 2024
概括
这项研究确定了调节Leishmania寄生虫吸收和生存的宿主激酶. 发现了新的激酶,这表明复杂的宿主激酶网络对于莱什曼尼亚感染至关重要.
科学领域:
- 免疫学 免疫学 免疫学
- 细胞生物学 细胞生物学
- 寄生虫学的寄生虫学
背景情况:
- 莱什马尼亚寄生虫在沙促生虫和哺乳动物促生虫之间交替存在.
- 细胞吸收前列腺细胞启动感染,需要在细胞体内存活.
研究的目的:
- 为了识别Leishmania的宿主激酶调节者,大细胞和大细胞的吸收和存活.
- 为了区分寄生虫的吸收机制与一般的细胞分裂.
主要方法:
- 一个基于图像的酶回归屏幕,使用38种酶抑制剂.
- 针对惰性珠子来补充受体3 (CR3) 或Fcγ受体 (FcR) 作为控制.
- 分析Leishmania amazonensis吸收和细胞内生存的宿主激酶调节.
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.
- 预测宿主激酶参与前虫转化为前虫和前虫存活.
- 发现的激酶优先调节寄生虫吸收而不是珠子吸收,这表明了不同的机制.
结论:
- 在Leishmania感染期间,多个相互连接的宿主激酶网络是必不可少的.
- 激酶的要求因受体结合和寄生虫生命周期阶段而异.
- 这些发现为研究Leishmania的宿主-病原体相互作用和激酶作用提供了资源.
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...


