Neisseria meningitidis differentially controls host cell motility through PilC1 and PilC2 components of type IV Pili.
Neisseria meningitidis differentially controls host cell motility through PilC1 and PilC2 components of type IV Pili.
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DOI：
10.1371/journal.pone.0006834
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发表时间：
2009-08-31
期刊：
影响因子：
3.7
通讯作者：
Meyer TF
中科院分区：
文献类型：
--
作者：
Morand PC;Drab M;Rajalingam K;Nassif X;Meyer TF
脑膜炎奈瑟菌是一种严格意义上的人类病原体，它有两个方面，因为无症状携带可不可预测地转变为暴发性感染。脑膜炎双球菌的发病依赖于细菌打破宿主上皮或内皮细胞屏障的能力。脑膜炎双球菌对人类来源的细胞具有高度限制性，但知之甚少，其机制允许其与细胞黏附。被包裹的和毒力强的脑膜炎球菌对人类细胞的黏附依赖于四型细菌菌毛(T4P)的表达，T4P触发强烈的宿主细胞信号。在脑膜炎球菌T4P的成分中，同时表达的PilC1和PilC2蛋白调节细菌表面的菌毛暴露，到目前为止，PilC1被认为是T4P介导的脑膜炎球菌与人类细胞黏附的特异性原因。与以前的报道相反，我们发现，脑膜炎球菌PilC2成分与PilC1一样，能够介导与人ME180上皮细胞的黏附，形成皮质斑块和F-肌动蛋白凝聚。然而，PilC1和PilC2对感染细胞的促进作用不同。细胞追踪分析表明，表达PilC2的脑膜炎双球菌导致感染细胞的活力严重降低，而当细胞感染表达PilC2的菌株时，情况并非如此。在PilC1介导的感染过程中，细胞中EGFR的总形式和磷酸化形式的数量都显著减少。相反，PilC2介导的感染对EGFR途径没有显著影响，这些特异性在不相关的脑膜炎球菌株中共享。这些结果表明，脑膜炎双球菌在存在不同细胞类型的特定微环境中进化出了一种高度区分不同黏附的工具。此外，通过同一分子的两个同时表达但受到明显调控的T4P相关变体(即PilC1和PilC2)的联合作用对细胞控制进行微调，为分析病原菌与人类宿主细胞之间的相互作用提供了一种新的模型。
Neisseria meningitidis is a strictly human pathogen that has two facets since asymptomatic carriage can unpredictably turn into fulminant forms of infection. Meningococcal pathogenesis relies on the ability of the bacteria to break host epithelial or endothelial cellular barriers. Highly restrictive, yet poorly understood, mechanisms allow meningococcal adhesion to cells of only human origin. Adhesion of encapsulated and virulent meningococci to human cells relies on the expression of bacterial type four pili (T4P) that trigger intense host cell signalling. Among the components of the meningococcal T4P, the concomitantly expressed PilC1 and PilC2 proteins regulate pili exposure at the bacterial surface, and until now, PilC1 was believed to be specifically responsible for T4P-mediated meningococcal adhesion to human cells. Contrary to previous reports, we show that, like PilC1, the meningococcal PilC2 component is capable of mediating adhesion to human ME180 epithelial cells, with cortical plaque formation and F-actin condensation. However, PilC1 and PilC2 promote different effects on infected cells. Cellular tracking analysis revealed that PilC1-expressing meningococci caused a severe reduction in the motility of infected cells, which was not the case when cells were infected with PilC2-expressing strains. The amount of both total and phosphorylated forms of EGFR was dramatically reduced in cells upon PilC1-mediated infection. In contrast, PilC2-mediated infection did not notably affect the EGFR pathway, and these specificities were shared among unrelated meningococcal strains. These results suggest that meningococci have evolved a highly discriminative tool for differential adhesion in specific microenvironments where different cell types are present. Moreover, the fine-tuning of cellular control through the combined action of two concomitantly expressed, but distinctly regulated, T4P-associated variants of the same molecule (i.e. PilC1 and PilC2) brings a new model to light for the analysis of the interplay between pathogenic bacteria and human host cells.
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DOI：
10.1083/jcb.200106148
发表时间：
2001-10-01
期刊：
The Journal of cell biology
影响因子：
--
作者：
Hoffmann I;Eugène E;Nassif X;Couraud PO;Bourdoulous S
通讯作者：
Bourdoulous S
影响因子：
56.9
作者：
Coureuil, Mathieu;Mikaty, Guillain;Nassif, Xavier
通讯作者：
Nassif, Xavier
影响因子：
3.1
作者：
Pujol, C;Eugene, E;Nassif, X
通讯作者：
Nassif, X
影响因子：
4.8
作者：
Källström, H;Islam, MS;Jonsson, AB
通讯作者：
Jonsson, AB
影响因子：
3.6
作者：
Morand, PC;Tattevin, P;Nassif, X
通讯作者：
Nassif, X