Pilus hijacking by a bacterial coaggregation factor critical for oral biofilm development

Pilus hijacking by a bacterial coaggregation factor critical for oral biofilm development
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DOI:
10.1073/pnas.1321417111
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发表时间:
2014-03-11
影响因子:
11.1
通讯作者:
Hung Ton-That
Hung Ton-That
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Reardon-Robinson, Melissa E.;Wu, Chenggang;Hung Ton-That

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牙菌斑是引起牙龈炎和牙周炎的高度复杂的生物膜,其形成需要许多口腔微生物之间的特异性粘附,包括口腔放线菌与口腔链球菌的共聚集,其有助于种子生物膜的形成。在这里,我们报告发现了一个关键的共聚集因子,这个过程。该蛋白被我们命名为共聚集因子A(coaggregationfactor A,CafA),是14种具有LPXTG基序的细胞表面蛋白之一。oris MG 1,其功能迄今未知。通过对这些基因的系统诱变和表型表征,我们发现放线菌/链球菌共聚集仅通过缺失cafA而被废除。随后的生物化学和细胞学实验表明,CafA构成了一种独特形式的2型菌毛的尖端,这种菌毛长期以来以其在共聚集中的作用而闻名。CafA在粘附中的直接和主要作用从CafA或针对CafA的抗体抑制共聚集的事实是明显的,而轴蛋白FimA或针对FimA的多克隆抗体没有影响。值得注意的是,FimA聚合被CafA和FimB基因的缺失所阻断,CafA和FimB是先前描述的2型菌毛的尖端蛋白。总之,这些结果表明,革兰氏阳性菌中一些不与菌毛基因簇相连的表面蛋白可能会劫持菌毛。这些独特的尖端蛋白显示在一个共同的菌毛轴可能有不同的生理功能。此外,革兰氏阳性细菌中的菌毛轴组件可能需要尖端,对于某些革兰氏阴性细菌皮利也是如此。
The formation of dental plaque, a highly complex biofilm that causes gingivitis and periodontitis, requires specific adherence among many oral microbes, including the coaggregation of Actinomyces oris with Streptococcus oralis that helps to seed biofilm development. Here, we report the discovery of a key coaggregation factor for this process. This protein, which we named coaggregation factor A (CafA), is one of 14 cell surface proteins with the LPXTG motif predicted in A. oris MG1, whose function was hitherto unknown. By systematic mutagenesis of each of these genes and phenotypic characterization, we found that the Actinomyces/Streptococcus coaggregation is only abolished by deletion of cafA. Subsequent biochemical and cytological experiments revealed that CafA constitutes the tip of a unique form of the type 2 fimbria long known for its role in coaggregation. The direct and predominant role of CafA in adherence is evident from the fact that CafA or an antibody against CafA inhibits coaggregation, whereas the shaft protein FimA or a polyclonal antibody against FimA has no effect. Remarkably, FimA polymerization was blocked by deletion of genes for both CafA and FimB, the previously described tip protein of the type 2 fimbria. Together, these results indicate that some surface proteins not linked to a pilus gene cluster in Gram-positive bacteria may hijack the pilus. These unique tip proteins displayed on a common pilus shaft may serve distinct physiological functions. Furthermore, the pilus shaft assembly in Gram-positive bacteria may require a tip, as is true for certain Gramnegative bacterial pili.