Host Proteasomal Degradation Generates Amino Acids Essential for Intracellular Bacterial Growth
Host Proteasomal Degradation Generates Amino Acids Essential for Intracellular Bacterial Growth
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DOI：
10.1126/science.1212868
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发表时间：
2011-12-16
期刊：
影响因子：
56.9
通讯作者：
Abu Kwaik, Yousef
中科院分区：
文献类型：
--
作者：
Price, Christopher T. D.;Al-Quadan, Tasneem;Abu Kwaik, Yousef
嗜肺军团菌在环境阿米巴和含军团菌空泡（LCV）内的人体细胞中增殖。导出的L.嗜肺菌通过宿主介导的法尼基化作用锚定在LCV膜上。在这里，我们报告说，宿主蛋白酶体降解的赖氨酸（48）连接的多泛素化蛋白，组装在LCV的AnkB，产生细胞内细菌增殖所需的氨基酸。通过补充氨基酸或半胱氨酸、丝氨酸、丙酮酸或柠檬酸的混合物，类似于通过遗传互补的拯救，可以拯救阿米巴和人类细胞内的ankB无效突变体在增殖中的严重缺陷。在小鼠肺内增殖中ankB突变体的缺陷在注射氨基酸或半胱氨酸的混合物后被挽救。因此，军团菌促进真核生物蛋白酶体降解，以产生所需的氨基酸作为碳和能源的细菌增殖在进化上遥远的主机。
Legionella pneumophila proliferates in environmental amoeba and human cells within the Legionella-containing vacuole (LCV). The exported AnkB F-box effector of L. pneumophila is anchored into the LCV membrane by host-mediated farnesylation. Here, we report that host proteasomal degradation of Lys(48)-linked polyubiquitinated proteins, assembled on the LCV by AnkB, generates amino acids required for intracellular bacterial proliferation. The severe defect of the ankB null mutant in proliferation within amoeba and human cells is rescued by supplementation of a mixture of amino acids or cysteine, serine, pyruvate, or citrate, similar to rescue by genetic complementation. Defect of the ankB mutant in intrapulmonary proliferation in mice is rescued upon injection of a mixture of amino acids or cysteine. Therefore, Legionella promotes eukaryotic proteasomal degradation to generate amino acids needed as carbon and energy sources for bacterial proliferation within evolutionarily distant hosts.