Transglutaminase 2 is essential for adherence of Porphyromonas gingivalis to host cells
Transglutaminase 2 is essential for adherence of Porphyromonas gingivalis to host cells
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DOI：
10.1073/pnas.1402740111
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发表时间：
2014-04-08
影响因子：
11.1
通讯作者：
Duncan, Margaret J.
中科院分区：
文献类型：
--
作者：
Boisvert, Heike;Lorand, Laszlo;Duncan, Margaret J.
牙龈卟啉单胞菌是牙周炎的主要致病菌，它也可能参与全身性疾病（动脉粥样硬化，类风湿性关节炎）的发展。牙龈卟啉单胞菌在与宿主细胞的表面组分结合后在口腔和牙龈上皮细胞上和内发现，宿主细胞作为细菌的受体。这项研究中提出的证据表明，转氨酶2（TG 2）在牙龈卟啉单胞菌粘附宿主细胞中起着关键作用。共聚焦显微镜的研究表明牙龈卟啉单胞菌与TG 2在HEp-2上皮细胞表面上共定位，在细菌附着位点处观察到TG 2簇。通过在HEp-2细胞中用siRNA沉默TG 2的表达，牙龈卟啉单胞菌缔合大大减少。该细菌不能很好地与产生少量表面TG 2的小鼠成纤维细胞系结合，但可以通过引入在质粒上表达的TG 2来恢复结合。TG 2可以与纤连蛋白（FN）形成非常紧密的复合物，并且这两种蛋白质的互补结合位点是已知的。模拟TG 2的主要FN结合序列的合成肽阻断TG 2-FN复合物的形成，并且高度有效地抑制牙龈卟啉单胞菌对宿主细胞的粘附。这些发现为细胞表面TG 2在细菌附着和随后的内化中的作用提供了证据。
Porphyromonas gingivalis is the major causative agent of periodontitis, and it may also be involved in the development of systemic diseases (atherosclerosis, rheumatoid arthritis). P. gingivalis is found on and within oral and gingival epithelial cells following binding to surface components of host cells, which serve as receptors for the bacterium. Evidence is presented in this study that shows that transglutaminase 2 (TG2) plays a critical role in the adherence of P. gingivalis to host cells. Studies of confocal microscopy indicate colocalization of P. gingivalis with TG2 on the surface of HEp-2 epithelial cells, with clusters of TG2 seen at bacterial attachment sites. By silencing the expression of TG2 with siRNA in HEp-2 cells, P. gingivalis association was greatly diminished. The bacterium does not bind well to a mouse fibroblast cell line that produces low amounts of surface TG2, but binding can be restored by introduction of TG2 expressed on a plasmid. TG2 can form very tight complexes with fibronectin (FN), and the complementary binding sites of the two proteins are known. A synthetic peptide that mimics the main FN-binding sequence of TG2 blocks the formation of TG2-FN complexes and is highly effective in inhibiting adherence of P. gingivalis to host cells. These findings provide evidence of a role for cell-surface TG2 in bacterial attachment and subsequent internalization.