Host metabolism regulates intracellular growth of Trypanosoma cruzi.
Host metabolism regulates intracellular growth of Trypanosoma cruzi.
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DOI：
10.1016/j.chom.2012.11.011
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发表时间：
2013-01-16
影响因子：
30.3
通讯作者：
Burleigh BA
中科院分区：
文献类型：
--
作者：
Caradonna KL;Engel JC;Jacobi D;Lee CH;Burleigh BA
细胞内病原体与宿主细胞的代谢偶联对宿主的成功定植至关重要。原生动物克氏锥虫细胞内感染导致人类恰加斯病的发生，但宿主细胞在感染过程中的功能贡献尚不清楚。在这里，基因组规模的功能筛查发现，以宿主能量产生、核苷酸代谢、蝶啶生物合成和脂肪酸氧化为中心的相互关联的代谢网络是推动克氏锥虫细胞内生长的关键过程。此外，宿主激酶Akt在各种细胞过程中起着至关重要的作用，对寄生虫的复制至关重要。这些宿主代谢途径或Akt依赖的信号通路中的靶向扰动调节了寄生虫的复制能力，突显了这种细胞内病原体对宿主不断变化的条件的适应性。这些发现确定了调节细胞内毛滴虫生长的关键细胞过程，并阐明了利用宿主途径限制毛滴虫感染的潜力。
Metabolic coupling of intracellular pathogens with host cells is essential for successful colonization of the host. Establishment of intracellular infection by the protozoan Trypanosoma cruzi leads to the development of human Chagas disease, yet the functional contributions of the host cell toward the infection process remain poorly characterized. Here, a genome-scale functional screen identified interconnected metabolic networks centered around host energy production, nucleotide metabolism, pteridine biosynthesis, and fatty acid oxidation as key processes that fuel intracellular T. cruzi growth. Additionally, the host kinase Akt, which plays essential roles in various cellular processes, was critical for parasite replication. Targeted perturbations in these host metabolic pathways or Akt-dependent signaling pathways modulated the parasite’s replicative capacity, highlighting the adaptability of this intracellular pathogen to changing conditions in the host. These findings identify key cellular process regulating intracellular T. cruzi growth and illuminate the potential to leverage host pathways to limit T. cruzi infection.
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影响因子：
7.3
作者：
Chuenkova, Marina V.;PereiraPerrin, Mercio
通讯作者：
PereiraPerrin, Mercio
影响因子：
4.1
作者：
Garg, N;Gerstner, A;Papaconstantinou, J
通讯作者：
Papaconstantinou, J
影响因子：
64.5
作者：
Kumar, Dhiraj;Nath, Lekha;Rao, Kanury V. S.
通讯作者：
Rao, Kanury V. S.
影响因子：
16.1
作者：
Ikeda M;Kato N
通讯作者：
Kato N
DOI：
10.1016/0020-711x(79)90065-x
发表时间：
1979-01-01
期刊：
INTERNATIONAL JOURNAL OF BIOCHEMISTRY
影响因子：
--
作者：
GUTTERIDGE, WE;GABORAK, M
通讯作者：
GABORAK, M