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首页> 外文期刊>Infection and immunity >RgpA-Kgp Peptide-Based Immunogens Provide Protection againstPorphyromonas gingivalis Challenge in a Murine Lesion Model
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RgpA-Kgp Peptide-Based Immunogens Provide Protection againstPorphyromonas gingivalis Challenge in a Murine Lesion Model

机译：RgpA-Kgp肽基免疫原为小鼠病变模型中的牙龈卟啉单胞菌挑战提供了保护。

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Porphyromonas gingivalis, a gram-negative bacterium, has been linked to the onset and progression of periodontitis, a chronic inflammatory disease of the supporting tissues of the teeth. A major virulence factor ofP. gingivalis is an extracellular complex of Arg- and Lys-specific proteinases and adhesins designated the RgpA-Kgp complex (formerly the PrtR-PrtK complex). In this study we show that the RgpA-Kgp complex, when used as an immunogen with incomplete Freund adjuvant (IFA), protects against challenge with invasive and noninvasive strains of P. gingivalis in the murine lesion model. We identified a variety of peptide vaccine candidates from the RgpA and Kgp polyprotein sequences that involved the putative active site histidine of both proteinases and five repeat motifs in the adhesin domains of both polyproteins implicated in aggregation and binding to host substrates, designated adhesin-binding motif (ABM) peptides. These peptides were synthesized using standard, solid-phase protocols for 9-fluorenylmethoxy carbonyl chemistry withS-acetylmercaptoacetic acid (SAMA) as the N-terminal residue. The SAMA-peptides were then conjugated to diphtheria toxoid and used with IFA to immunize BALB/c mice. Both active-site peptides and three of the five ABM peptides gave protection (P< 0.005) against challenge with P. gingivalis in the murine lesion model. The three ABM peptide sequences that conferred protection exist within a 100-residue span in the RgpA44 and Kgp39 adhesins of the RgpA-Kgp complex. Protective anti-RgpA-Kgp complex mouse antisera recognized the RgpA27, Kgp39, and RgpA44 adhesins in an immunoblot. Epitope mapping of the RgpA27 adhesin using the protective anti-RgpA-Kgp antisera identified a major protective epitope that mapped immediately N terminal to one of the protective ABM peptides in the 100-residue span in RgpA44 and Kgp39. This identified protective epitope contains clusters of basic residues spatially surrounded by hydrophobic amino acids, a finding which is characteristic of a heparin binding motif.
机译：革兰氏阴性细菌 Porphyromonas gingivalis 与牙周炎的发病和发展有关，牙周炎是一种牙齿支持组织的慢性炎症性疾病。主要毒力因子为 P。齿龈炎是Arg和Lys特异性蛋白酶和粘附素的细胞外复合物，称为RgpA-Kgp复合物（以前称为PrtR-PrtK复合物）。在这项研究中，我们表明RgpA-Kgp复合物用作不完全弗氏佐剂（IFA）的免疫原时，可以防止侵入性和非侵入性 P菌株的攻击。鼠病变模型中的牙龈炎。我们从RgpA和Kgp多蛋白序列中鉴定了多种肽疫苗候选物，这些肽疫苗涉及两种蛋白酶的假定活性位点组氨酸和两种多蛋白的粘附素结构域中的五个重复基序，牵涉到聚集和结合宿主底物，称为粘附素结合基序（ABM）肽。这些肽是使用9-芴基甲氧基羰基化学的标准固相方法合成的，其中以 S -乙酰巯基乙酸（SAMA）为N末端残基。然后将SAMA-肽缀合至白喉类毒素，并与IFA一起用于免疫BALB / c小鼠。活性位点肽和五个ABM肽中的三个都提供保护（ P <0.005）以抵抗 P的攻击。鼠病变模型中的牙龈炎。 RgpA-Kgp复合体的RgpA44和Kgp39粘附素的100个残基跨度内有三个提供保护的ABM肽序列。保护性抗RgpA-Kgp复合物小鼠抗血清在免疫印迹中识别RgpA27，Kgp39和RgpA44粘附素。使用保护性抗RgpA-Kgp抗血清对RgpA27粘附素进行的表位作图确定了一个主要的保护性表位，该表位立即在RgpA44和Kgp39的100个残基跨度中的N末端与保护性ABM肽之一​​相对应。该鉴定的保护性表位包含在空间上被疏水性氨基酸包围的碱性残基簇，该发现是肝素结合基序的特征。

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