Role of host GTPases in infection by Listeria monocytogenes.
Role of host GTPases in infection by Listeria monocytogenes.
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DOI：
10.1111/cmi.12324
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发表时间：
2014-09
影响因子：
3.4
通讯作者：
Dowd GC
中科院分区：
文献类型：
--
作者：
Ireton K;Rigano LA;Dowd GC
细菌病原体单核增生李斯特菌诱导内化进入哺乳动物细胞，并利用肌动蛋白为基础的运动在组织内传播。李斯特菌通过利用或拮抗几种宿主gtp酶来完成细胞内的生命周期。细菌表面蛋白InlA或InlB介导其内化进入人体细胞。这两种摄取模式都需要一个由GTPase Rac1、成核促进因子和Arp2/3复合物组成的宿主肌动蛋白聚合途径。除了Rac1外，inlb介导的内化还包括抑制GTPase Arf6和参与Dynamin和septin家族GTPase。摄取后，李斯特菌被包裹在宿主吞噬体中。细菌蛋白GAPDH使人GTPase Rab5失活，从而延缓吞噬体获得抗菌特性。在细菌诱导的吞噬体破坏后，细胞质李斯特菌使用表面蛋白ActA来刺激肌动蛋白为基础的运动。GTPase动力蛋白2降低了微管的密度，否则微管会限制细菌的运动。当活动的李斯特菌将宿主的质膜重塑成被邻近细胞吞噬的突起时，细胞间的传播就发生了。人类GTPase Cdc42、其激活物Tuba和其效应物N-WASP形成一个复合物，具有限制李斯特菌突起的潜力。细菌通过抑制Cdc42-GTP或Tuba/N-WASP相互作用的两个微生物因子克服了这一限制。
The bacterial pathogen Listeria monocytogenes induces internalization into mammalian cells and uses actin-based motility to spread within tissues. Listeria accomplishes this intracellular life cycle by exploiting or antagonizing several host GTPases. Internalization into human cells is mediated by the bacterial surface proteins InlA or InlB. These two modes of uptake each require a host actin polymerization pathway comprised of the GTPase Rac1, nucleation promotion factors, and the Arp2/3 complex. In addition to Rac1, InlB-mediated internalization involves inhibition of the GTPase Arf6 and participation of Dynamin and septin family GTPases. After uptake, Listeria is encased in host phagosomes. The bacterial protein GAPDH inactivates the human GTPase Rab5, thereby delaying phagosomal acquisition of antimicrobial properties. After bacterial-induced destruction of the phagosome, cytosolic Listeria uses the surface protein ActA to stimulate actin-based motility. The GTPase Dynamin 2 reduces the density of microtubules that would otherwise limit bacterial movement. Cell-to-cell spread results when motile Listeria remodel the host plasma membrane into protrusions that are engulfed by neighboring cells. The human GTPase Cdc42, its activator Tuba, and its effector N-WASP form a complex with the potential to restrict Listeria protrusions. Bacteria overcome this restriction through two microbial factors that inhibit Cdc42-GTP or Tuba/N-WASP interaction.