MRC Centre for Molecular Microbiology and Infection, Department of Life Sciences, Imperial College London, London, UK.
EA7361 'Structure, dynamic, function and expression of broad spectrum β-lactamases', Faculty of Medicine, Paris-Sud University, LabEx Lermit, Le Kremlin-Bicêtre, France.
Nat Microbiol. 2018 Mar;3(3):378-386. doi: 10.1038/s41564-018-0109-7. Epub 2018 Feb 5.
Recent studies highlight that bacterial pathogens can reprogram target cells by influencing epigenetic factors. The type III secretion system (T3SS) is a bacterial nanomachine that resembles a syringe on the bacterial surface. The T3SS 'needle' delivers translocon proteins into eukaryotic cell membranes, subsequently allowing injection of bacterial effectors into the cytosol. Here we show that Pseudomonas aeruginosa induces early T3SS-dependent dephosphorylation and deacetylation of histone H3 in eukaryotic cells. This is not triggered by any of the P. aeruginosa T3SS effectors, but results from the insertion of the PopB-PopD translocon into the membrane. This suggests that the P. aeruginosa translocon is a genuine T3SS effector acting as a pore-forming toxin. We visualized the translocon plugged into the host cell membrane after the bacterium has left the site of contact, and demonstrate that subsequent ion exchange through this pore is responsible for histone H3 modifications and host cell subversion.
最近的研究强调，细菌病原体可以通过影响表观遗传因素来重新编程靶细胞。III 型分泌系统（T3SS）是一种细菌纳米机器，类似于细菌表面的注射器。T3SS 的“针”将转位蛋白输送到真核细胞膜中，随后允许将细菌效应蛋白注入细胞质。在这里，我们表明铜绿假单胞菌诱导真核细胞中早期 T3SS 依赖性组蛋白 H3 的去磷酸化和去乙酰化。这不是由任何铜绿假单胞菌 T3SS 效应蛋白触发的，而是由于 PopB-PopD 转位蛋白插入到膜中。这表明铜绿假单胞菌转位蛋白是一种真正的 T3SS 效应蛋白，充当孔形成毒素。我们在细菌离开接触部位后观察到转位蛋白插入宿主细胞膜中，并证明随后通过该孔的离子交换是组蛋白 H3 修饰和宿主细胞颠覆的原因。
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