Impact of Porphyromonas gingivalis Peptidylarginine Deiminase on Bacterial Biofilm Formation, Epithelial Cell Invasion, and Epithelial Cell Transcriptional Landscape.
Impact of Porphyromonas gingivalis Peptidylarginine Deiminase on Bacterial Biofilm Formation, Epithelial Cell Invasion, and Epithelial Cell Transcriptional Landscape.
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DOI：
10.1038/s41598-018-32603-y
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发表时间：
2018-09-20
影响因子：
4.6
通讯作者：
Mydel P
中科院分区：
文献类型：
--
作者：
Aliko A;Kamińska M;Bergum B;Gawron K;Benedyk M;Lamont RJ;Malicki S;Delaleu N;Potempa J;Mydel P
肽基精氨酸脱亚胺酶（PPAD）是致病性卟啉单胞菌特别是牙龈卟啉单胞菌特有的毒力因子。从机制上讲，PPAD活性与Arg特异性牙龈卟啉菌蛋白酶一起产生具有瓜氨酸化C末端的蛋白片段。此类多肽是潜在的从头表位，其是类风湿性关节炎的关键驱动因素。这个过程可能是类风湿关节炎和牙周炎之间观察到的临床关联的基础。然而，PPAD在牙龈卟啉单胞菌宿主定植中的作用以及随后在引发牙周炎中的作用尚不清楚。因此，本研究的目的是描绘PPAD在细菌生物膜形成中的作用，并确定牙龈角质形成细胞对细菌的粘附、侵袭和宿主反应是否取决于PPAD活性。我们研究了这些方面使用PPAD-主管和PPAD-无能的牙龈卟啉单胞菌菌株，并证明，无论是生物膜的形成，也不是它的组成是由PPAD活性的影响。类似地，流式细胞术显示PPAD不影响牙龈卟啉单胞菌粘附并随后侵入角质形成细胞的能力。然而，基因表达模式的网络分析揭示了一组对PPAD活性敏感的宿主基因（CXCL 8、IL 36 G、CCL 20和IL 1B）。这些基因可被分类为属于白细胞介素1系统的有效免疫调节剂，或淋巴细胞和嗜中性粒细胞的化学引诱物。因此，我们得出结论，PPAD，虽然它是一种有效的调节免疫反应，不影响细菌生物膜的形成或牙龈卟啉单胞菌粘附和侵入牙龈上皮细胞的能力。
Peptidylarginine deiminase (PPAD) is a virulence factor unique to pathogenic Porphyromonas species, especially P. gingivalis. Mechanistically, PPAD activity, in conjunction with Arg-specific gingipains, generates protein fragments with citrullinated C-termini. Such polypeptides are potential de novo epitopes that are key drivers of rheumatoid arthritis. This process could underlie the observed clinical association between rheumatoid arthritis and periodontitis. However, the role of PPAD in host colonization by P. gingivalis and, subsequently, in triggering periodontitis is not known. Therefore, the aim of the current study was to delineate the role of PPAD in bacterial biofilm formation, and to define whether adherence to, invasion of, and host responses to bacteria of gingival keratinocytes depend on PPAD activity. We studied these aspects using PPAD-competent and PPAD-incompetent strains of P. gingivalis, and demonstrated that neither biofilm formation nor its composition was affected by PPAD activity. Similarly, flow cytometry revealed that PPAD did not impact the ability of P. gingivalis to adhere to and, subsequently, invade keratinocytes. Network analyses of gene expression patterns, however, revealed a group of host genes that were sensitive to PPAD activity (CXCL8, IL36G, CCL20, and IL1B). These genes can be categorized as potent immune modulators belonging to the interleukin 1 system, or chemoattractants of lymphocytes and neutrophils. Thus, we conclude that PPAD, although it is a potent modulator of the immune response, does not affect bacterial biofilm formation or the ability of P. gingivalis to adhere to and invade gingival epithelial cells.
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Keystone-Pathogen假设。
DOI：
10.1038/nrmicro2873
发表时间：
2012-10
期刊：
Nature reviews. Microbiology
影响因子：
--
作者：
通讯作者：
--
影响因子：
6.7
作者：
Allam, Jean-Pierre;Duan, Yonggang;Novak, Natalija
通讯作者：
Novak, Natalija
影响因子：
2.8
作者：
Lamont, RJ;El-Sabaeny, A;Demuth, DR
通讯作者：
Demuth, DR
影响因子：
3.5
作者：
Moffatt-Jauregui CE;Robinson B;de Moya AV;Brockman RD;Roman AV;Cash MN;Culp DJ;Lamont RJ
通讯作者：
Lamont RJ
重新审视佩奇和施罗德模型：40 年后牙周宿主反应的好、坏和未知。
影响因子：
18.6
作者：
Hajishengallis G;Korostoff JM
通讯作者：
Korostoff JM