There's no place like OM: Vesicular sorting and secretion of the peptidylarginine deiminase of Porphyromonas gingivalis.
There's no place like OM: Vesicular sorting and secretion of the peptidylarginine deiminase of Porphyromonas gingivalis.
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DOI：
10.1080/21505594.2017.1421827
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发表时间：
2018-01-01
期刊：
影响因子：
5.2
通讯作者：
van Dijl JM
中科院分区：
文献类型：
--
作者：
Gabarrini G;Palma Medina LM;Stobernack T;Prins RC;du Teil Espina M;Kuipers J;Chlebowicz MA;Rossen JWA;van Winkelhoff AJ;van Dijl JM
牙龈卟啉单胞菌是引起牙周炎的主要病原菌之一，近年来被认为是自身免疫性疾病类风湿性关节炎的潜在病因。特别是，牙龈卟啉单胞菌的肽基精氨酸脱亚胺酶（PPAD）与某些宿主蛋白的瓜氨酸化以及随后出现的抗瓜氨酸化蛋白的抗体有关，这可能在类风湿性关节炎的病因学中发挥作用。本研究的目的是调查PPAD的细胞外定位在一个大面板的临床牙龈卟啉单胞菌分离株。在这里，我们表明所有分离株都产生PPAD。在大多数情况下，PPAD大量存在于由牙龈卟啉单胞菌大量产生的分泌外膜囊泡（OMV）中，并且在较小程度上以可溶性分泌状态存在。有趣的是，一小部分临床分离株显示OMV结合PPAD水平大幅降低，并以可溶状态分泌大部分这种酶。后一种表型与PPAD中位置373处的赖氨酸残基严格相关，暗示PPAD中该位置处更常见的谷氨酰胺残基与OMV相关。此外，一个分离株显示严重限制囊泡。总之，我们的研究结果首次表明，牙龈卟啉单胞菌与人类宿主的相互作用既不需要PPAD与囊泡的主要联系，也不需要牙龈卟啉单胞菌囊泡形成本身。
The oral pathogen Porphyromonas gingivalis is one of the major periodontal agents and it has been recently hailed as a potential cause of the autoimmune disease rheumatoid arthritis. In particular, the peptidylarginine deiminase enzyme of P. gingivalis (PPAD) has been implicated in the citrullination of certain host proteins and the subsequent appearance of antibodies against citrullinated proteins, which might play a role in the etiology of rheumatoid arthritis. The aim of this study was to investigate the extracellular localization of PPAD in a large panel of clinical P. gingivalis isolates. Here we show that all isolates produced PPAD. In most cases PPAD was abundantly present in secreted outer membrane vesicles (OMVs) that are massively produced by P. gingivalis, and to minor extent in a soluble secreted state. Interestingly, a small subset of clinical isolates showed drastically reduced levels of the OMV-bound PPAD and secreted most of this enzyme in the soluble state. The latter phenotype is strictly associated with a lysine residue at position 373 in PPAD, implicating the more common glutamine residue at this position in PPAD association with OMVs. Further, one isolate displayed severely restricted vesiculation. Together, our findings show for the first time that neither the major association of PPAD with vesicles, nor P. gingivalis vesiculation per se, are needed for P. gingivalis interactions with the human host.
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影响因子：
27.4
作者：
Konig MF;Paracha AS;Moni M;Bingham CO 3rd;Andrade F
通讯作者：
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Potempa, J
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de Smit, M. J.;Brouwer, E.;van Winkelhoff, A. J.
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van Winkelhoff, A. J.