PilX, a pilus-associated protein essential for bacterial aggregation, is a key to pilus-facilitated attachment of Neisseria meningitidis to human cells

PilX, a pilus-associated protein essential for bacterial aggregation, is a key to pilus-facilitated attachment of Neisseria meningitidis to human cells
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DOI:
10.1111/j.1365-2958.2004.04372.x
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发表时间:
2005-01-01
影响因子:
3.6
通讯作者:
Pelicic, V
Pelicic, V
中科院分区:
生物学2区
文献类型:
--
作者:
Hélaine, S;Carbonnelle, E;Pelicic, V

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致病性奈瑟菌与人类细胞的附着,其中IV型菌毛(Tfp)起着关键但不完全确定的作用,取决于这些细菌与靶细胞建立接触的能力,也取决于细菌间的相互作用。为了提高我们对脑膜炎奈瑟菌粘附人类细胞的分子机制的理解,我们筛选了一组明确的突变体,用于那些对人类细胞系的附着减少的突变体。除了强调Tfp在这一过程中的核心作用外,该分析还发现了一种被称为pilX的新基因中断的突变体,该突变体显示出与非毛状突变体一样的粘附性受损,但在数量和质量上均未改变纤维。此外,编码一种与Tfp纤维结合的类似pilX的基因,也被发现对细菌聚集至关重要。我们在这里提供了一些证据,表明PilX具有固有的聚集性,但没有粘附性,并且由于缺乏细菌间的相互作用,PilX突变体的粘附细菌数量减少。这些数据扩展了目前关于tfp促进脑膜炎奈索菌粘附人类细胞的模型,表明毛主要通过介导细菌之间的合作而导致净初始粘附的增加,这一发现得到了支持,即在机械去除细菌聚集体后,可以在野生型(WT)遗传背景中观察到对初始粘附的主要影响。
The attachment of pathogenic Neisseria species to human cells, in which type IV pili (Tfp) play a key but incompletely defined role, depends on the ability of these bacteria to establish contacts with the target cells but also interbacterial interactions. In an effort to improve our understanding of the molecular mechanisms of N. meningitidis adherence to human cells, we screened a collection of defined mutants for those presenting reduced attachment to a human cell line. Besides underscoring the central role of Tfp in this process, this analysis led to the identification of mutants interrupted in a novel gene termed pilX, that displayed an adherence as impaired as that of a non-piliated mutant but quantitatively and qualitatively unaltered fibres. Moreover, the pilX gene, which encodes a pilin-like protein that copurifies with Tfp fibres, was also found to be essential for bacterial aggregation. We provide here several piece of evidence suggesting that PilX has intrinsic aggregative but no adhesive properties and that the reduced numbers of adherent bacteria seen with a pilX mutant result from the absence of interbacterial interactions. These data extend the current model for Tfp-facilitated adherence of N. meningitidis to human cells by suggesting that the pili lead to an increase in net initial adherence primarily by mediating a cooperation between the bacteria, which is supported by the finding that a major effect on initial adherence could be observed in a wild-type (WT) genetic background after a mechanical removal of the bacterial aggregates.