Institut Pasteur, Unité des Interactions Bactéries-Cellules, Paris F-75015, France.
Infect Immun. 2011 Jul;79(7):2839-46. doi: 10.1128/IAI.01243-10. Epub 2011 Apr 11.
Chromatin modification triggered by bacteria is a newly described mechanism by which pathogens impact host transcription. Listeria monocytogenes dephosphorylates histone H3 through the action of listeriolysin O (LLO); however, the underlying mechanism is unknown. Here we show that an unrelated pore-forming toxin, Aeromonas aerolysin, also provokes H3 dephosphorylation (dePH3). As reported for aerolysin, we show that LLO and related toxins induce a pore-dependent K(+) efflux and that this efflux is the signal required for dePH3. In addition, LLO-induced K(+) efflux activates caspase-1. However, we demonstrate that dePH3 is unlinked to this activation. Therefore, our study unveils K(+) efflux as an important signal leading to two independent events critical for infection, inflammasome activation and histone modification.
细菌引发的染色质修饰是病原体影响宿主转录的一种新描述的机制。李斯特菌通过李斯特菌溶血素 O (LLO)的作用使组蛋白 H3 去磷酸化；然而，其潜在机制尚不清楚。在这里，我们发现一种不相关的孔形成毒素，气单胞菌 aerolysin，也能引发 H3 去磷酸化 (dePH3)。与 aerolysin 报道的情况一样，我们表明 LLO 和相关毒素诱导依赖孔的 K(+)外流，并且这种外流是 dePH3 所必需的信号。此外，LLO 诱导的 K(+)外流激活半胱天冬酶-1。然而，我们证明 dePH3 与这种激活无关。因此，我们的研究揭示了 K(+)外流作为一个重要信号，导致感染过程中两个独立的关键事件，即炎症小体激活和组蛋白修饰。
