Selective subversion of autophagy complexes facilitates completion of the Brucella intracellular cycle.

Selective subversion of autophagy complexes facilitates completion of the Brucella intracellular cycle.
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DOI:
10.1016/j.chom.2011.12.002
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发表时间:
2012-01-19
影响因子:
30.3
通讯作者:
Celli J
Celli J
中科院分区:
医学1区
文献类型:
--
作者:
Starr T;Child R;Wehrly TD;Hansen B;Hwang S;López-Otin C;Virgin HW;Celli J

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自噬是一种细胞降解过程,可以通过将细胞内的微生物运送到溶酶体进行破坏来捕获和消除它们。然而,病原体已经进化出了颠覆这一过程的机制。细胞内的布鲁氏菌通过形成含有布鲁氏菌的空泡(BCV)来确保其生存,该空泡从胞内室运输到内质网(ER),细菌在内质网中增殖。我们表明,布鲁氏菌在内质网中复制之后,BCV转换为具有自噬特征的隔室(ABCV)。虽然布鲁氏菌在自噬缺陷细胞中向内质网的运输没有受到影响,但aBCV的形成需要自噬启动蛋白ULK1、Beclin 1和ATG14L以及PI3-激酶活性。然而,aBCV的形成不依赖于自噬延伸蛋白ATG5、ATG16L1、ATG4B、ATG7和LC3B。此外,布鲁氏菌需要aBCV来完成细胞内的生命周期和细胞间的传播,这表明布鲁氏菌选择性地利用自噬起始复合体来颠覆宿主清除和促进感染。
Autophagy is a cellular degradation process that can capture and eliminate intracellular microbes by delivering them to lysosomes for destruction. However, pathogens have evolved mechanisms to subvert this process. The intracellular bacteria Brucella abortus ensures its survival by forming the Brucella-containing vacuole (BCV) that traffics from the endocytic compartment to the endoplasmic reticulum (ER), where the bacterium proliferates. We show that Brucella replication in the ER is followed by BCV conversion into a compartment with autophagic features (aBCV). While Brucella trafficking to the ER was unaffected in autophagy-deficient cells, aBCV formation required the autophagy initiation proteins ULK1, Beclin 1 and ATG14L, and PI3-kinase activity. However, aBCV formation was independent of the autophagy elongation proteins ATG5, ATG16L1, ATG4B, ATG7 and LC3B. Furthermore, aBCVs were required to complete the intracellular Brucella lifecycle and for cell-to-cell spreading, demonstrating that Brucella selectively co-opts autophagy initiation complexes to subvert host clearance and promote infection.
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