Identification of Streptococcus cristatus peptides that repress expression of virulence genes in Porphyromonas gingivalis.
Identification of Streptococcus cristatus peptides that repress expression of virulence genes in Porphyromonas gingivalis.
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DOI：
10.1038/s41598-017-01551-4
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发表时间：
2017-05-03
影响因子：
4.6
通讯作者：
Xie H
中科院分区：
文献类型：
--
作者：
Ho MH;Lamont RJ;Xie H
牙菌斑是一种复杂的多物种生物膜，是牙周病的直接先兆。牙周病原体，如牙龈卟啉单胞菌的毒力，是在这种多微生物群落的背景下表达的。我们曾报道过冠状链球菌与牙龈卟啉单胞菌之间存在拮抗关系，并鉴定了冠状链球菌的精氨酸脱亚胺酶（ArcA）。cristatus作为信号分子，牙龈卟啉单胞菌通过抑制FimA蛋白的表达和产生来响应。在这里，我们证明了牙龈卟啉单胞菌和S。鸡冠是细胞间通讯所必需的。发现牙龈卟啉单胞菌的两个表面蛋白PGN_0294和PGN_0806与S.鸡冠花使用肽阵列分析，我们鉴定了ArcA的几个牙龈卟啉单胞菌结合位点，从而发现了具有ArcA天然序列的11聚体肽，该肽抑制了菌毛和牙龈蛋白酶的表达。这些数据表明，ArcA的功能基序足以选择性地改变牙龈卟啉单胞菌中的毒力基因表达，并且PGN_0294和PGN_0806可以充当ArcA的受体。我们的研究结果为将来合理设计干扰牙龈卟啉单胞菌诱导的致病菌群的启动和形成的药物提供了分子基础。
Dental plaque is a complex multispecies biofilm, and is a direct precursor of periodontal disease. The virulence of periodontal pathogens, such as Porphyromonas gingivalis, is expressed in the context of this polymicrobial community. Previously, we reported an antagonistic relationship between Streptococcus cristatus and P. gingivalis, and identified arginine deiminase (ArcA) of S. cristatus as the signaling molecule to which P. gingivalis responds by repressing the expression and production of FimA protein. Here we demonstrate that direct interaction between P. gingivalis and S. cristatus is necessary for the cell-cell communication. Two surface proteins of P. gingivalis, PGN_0294 and PGN_0806, were found to interact with S. cristatus ArcA. Using a peptide array analysis, we identified several P. gingivalis-binding sites of ArcA, which led to the discovery of an 11-mer peptide with the native sequence of ArcA that repressed expression of fimbriae and of gingipains. These data indicate that a functional motif of ArcA is sufficient to selectively alter virulence gene expression in P. gingivalis, and PGN_0294 and PGN_0806 may serve as receptors for ArcA. Our findings provide a molecular basis for future rational design of agents that interfere with the initiation and formation of a P. gingivalis-induced pathogenic community.