Identification of proteins involved in the anti-inflammatory properties of Propionibacterium freudenreichii by means of a multi-strain study.

Identification of proteins involved in the anti-inflammatory properties of Propionibacterium freudenreichii by means of a multi-strain study.
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DOI:
10.1038/srep46409
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发表时间:
2017-04-13
期刊:
影响因子:
4.6
通讯作者:
Falentin H
Falentin H
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Deutsch SM;Mariadassou M;Nicolas P;Parayre S;Le Guellec R;Chuat V;Peton V;Le Maréchal C;Burati J;Loux V;Briard-Bion V;Jardin J;Plé C;Foligné B;Jan G;Falentin H

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费氏丙酸杆菌(一种乳制品发酵剂)在食用时在瑞士型奶酪中每克可达到近 109 个丙酸杆菌数量。它也作为益生菌食用,具有菌株依赖性抗炎特性,由诱导白细胞中 IL-10 的表面蛋白介导。我们选择了 23 种具有不同抗炎潜力的菌株,以鉴定所涉及的蛋白质。经过比较基因组分析后,其中 12 个菌株通过表面蛋白质组学进行了进一步分析,其中 8 个菌株进一步进行了转录组学分析。然后将组学数据与通过 IL-10 诱导评估的抗炎潜力相关联。这种比较组学策略强调了进一步进行基因失活验证的候选基因。该验证证实了表面蛋白的贡献,包括 SlpB 和 SlpE,这两种具有 SLH 结构域的蛋白已知可介导细胞壁的非共价锚定。有趣的是,HsdM3(预计为细胞质并参与 DNA 修饰)被证明有助于抗炎活性。最后,我们证明单一蛋白质无法解释菌株的抗炎特性。因此,这些特性是由表面蛋白和细胞质蛋白的不同组合产生的,具体取决于菌株。我们对免疫调节分子基础的深入了解将使我们能够对具有抗炎特性的细菌资源进行相关筛选。
Propionibacterium freudenreichii, a dairy starter, can reach a population of almost 109 propionibacteria per gram in Swiss-type cheese at the time of consumption. Also consumed as a probiotic, it displays strain-dependent anti-inflammatory properties mediated by surface proteins that induce IL-10 in leukocytes. We selected 23 strains with varied anti-inflammatory potentials in order to identify the protein(s) involved. After comparative genomic analysis, 12 of these strains were further analysed by surface proteomics, eight of them being further submitted to transcriptomics. The omics data were then correlated to the anti-inflammatory potential evaluated by IL-10 induction. This comparative omics strategy highlighted candidate genes that were further subjected to gene-inactivation validation. This validation confirmed the contribution of surface proteins, including SlpB and SlpE, two proteins with SLH domains known to mediate non-covalent anchorage to the cell-wall. Interestingly, HsdM3, predicted as cytoplasmic and involved in DNA modification, was shown to contribute to anti-inflammatory activity. Finally, we demonstrated that a single protein cannot explain the anti-inflammatory properties of a strain. These properties therefore result from different combinations of surface and cytoplasmic proteins, depending on the strain. Our enhanced understanding of the molecular bases for immunomodulation will enable the relevant screening for bacterial resources with anti-inflammatory properties.