Fusobacterium nucleatum Outer Membrane Proteins Fap2 and RadD Induce Cell Death in Human Lymphocytes
Fusobacterium nucleatum Outer Membrane Proteins Fap2 and RadD Induce Cell Death in Human Lymphocytes
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DOI：
10.1128/iai.00567-10
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发表时间：
2010-11-01
影响因子：
3.1
通讯作者：
Shi, Wenyuan
中科院分区：
文献类型：
--
作者：
Kaplan, Christopher W.;Ma, Xiaoyuan;Shi, Wenyuan
人类淋巴细胞中细菌诱导的细胞死亡是致病菌的重要毒力因子。先前发现的细菌诱导细胞死亡的机制主要基于细菌蛋白向靶宿主细胞的转移，例如通过I、II和VI型分泌系统分泌的毒素或通过III、IV和Vb型分泌系统注射的效应蛋白。在这里，我们报告了革兰氏阴性口腔病原体具核梭杆菌通过两种外膜蛋白（OMP）Fap2和RadD诱导人类淋巴细胞细胞死亡的机制，这两种蛋白共享与自转运蛋白分泌系统（Va型分泌系统）同源的区域。遗传和生理学研究表明，两种 OMP 失活会导致 Jurkat 细胞触发细胞死亡的能力显着降低，而相应的双突变体几乎完全减弱。其他生化和分子分析表明，无细胞具核梭杆菌膜足以诱导 Jurkat 细胞死亡，这表明不需要主动过程或效应蛋白转移来诱导真核细胞死亡。
Bacterially induced cell death in human lymphocytes is an important virulence factor for pathogenic bacteria. Previously discovered mechanisms of bacterially induced cell death are predominantly based on the transfer of bacterial proteins to the target host cell, such as the toxins secreted through type I, II, and VI secretion systems or effector proteins injected through type III, IV, and Vb secretion systems. Here, we report a mechanism employed by the Gram-negative oral pathogen Fusobacterium nucleatum for cell death induction of human lymphocytes via two outer membrane proteins (OMPs), Fap2 and RadD, which share regions homologous to autotransporter secretion systems (type Va secretion systems). Genetic and physiological studies established that inactivation of the two OMPs led to significantly reduced ability to trigger cell death in Jurkat cells, while the corresponding double mutant was almost completely attenuated. Additional biochemical and molecular analyses demonstrated that cell-free F. nucleatum membranes are sufficient to induce cell death in Jurkat cells, suggesting that no active process or effector protein transfer was necessary to induce eukaryotic cell death.