3-Phenyllactic acid generated in medicinal plant extracts fermented with plant-derived lactic acid bacteria inhibits the biofilm synthesis of Aggregatibacter actinomycetemcomitans.
3-Phenyllactic acid generated in medicinal plant extracts fermented with plant-derived lactic acid bacteria inhibits the biofilm synthesis of Aggregatibacter actinomycetemcomitans.
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DOI：
10.3389/fmicb.2022.991144
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发表时间：
2022
影响因子：
5.2
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中科院分区：
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在本研究中，研究了PLA对牙周病原菌伴放线聚集菌（A. actinomycetemcomitans）、生物膜和毒力相关基因的影响。我们证实，从植物源中分离出的两种乳酸菌 (LAB) 菌株，即植物乳杆菌 MSC-C2 和戊糖片球菌 K40，在添加作为 PLA 前体的苯丙酮酸 (PPA) 时，可将 PLA 分泌到 de Man、Rogosa & Sharpe (MRS) 肉汤中。此外，当每种 LAB 菌株和每种补充有 PPA 的提取物使用时，两种药用植物提取物芍药 (PR) 和红花 (CT) 的发酵液中都会产生 PLA。我们确定PLA对A. actinomycetemcomitans的最低抑制浓度（MIC）为20mM。 PLA 显着减少生物膜形成并抑制 pgA、ltxA 和 cdtB 基因的转录，这些基因分别编码生物膜基质的聚 N-乙酰氨基葡萄糖 (PGA) 多糖以及外毒素白细胞毒素和细胞致死膨胀毒素 (CDT)。通过向 MRS 肉汤中添加 PPA，MSC-C2 和 K40 菌株产生的 PLA 增加了数倍。发酵液提取物的抗生物膜作用与 PLA 浓度的增加成正比，而累积效果比单独的 PLA 更高，表明 PLA 和其他代谢物（例如乳酸 (LA)）的组合作用。在两种药用植物中，添加 PPA 后产生的 PLA 在两种 LAB 菌株的 PR 提取物中含量较高。 PR提取物中MSC-C2菌株的PLA产量达到4.8±0.23mM，明显高于添加1mg/ml PPA的MRS肉汤中的PLA产量（3.88±0.12mM）。发酵的 PR 提取物抑制生物膜形成的活性明显很高。发酵 PR 提取物中形成的 PLA 与 pgA、ltxA 和 cdtB 一起下调编码 dspB 基因的分散素 B。总之，本研究表明 PLA 对 A. actinomycetemcomitans 生物膜和毒力基因具有良好的活性。此外，PLA 和药用植物提取物的组合效应可以通过特定植物源 LAB 菌株的发酵来实现。
In the present study, the effect of PLA on a periodontic pathogen, Aggregatibacter actinomycetemcomitans (A. actinomycetemcomitans), the biofilm, and virulence-related genes was investigated. We confirmed that two lactic acid bacteria (LAB) strains isolated from plant sources, Lactiplantibacillus plantarum MSC-C2 and Pediococcus pentosaceus K40, secrete PLA into the de Man, Rogosa & Sharpe (MRS) broth when supplemented with phenyl pyruvic acid (PPA) as a precursor to PLA. Moreover, PLA was generated in the fermentation broths of two medicinal plant extracts, Paeonia lactiflora Pall (PR) and Carthamus tinctorius (CT), when used by each LAB strain and each extract supplemented with PPA. We determined that the minimum inhibitory concentration (MIC) of PLA against A. actinomycetemcomitans was 20 mM. PLA significantly decreased biofilm formation and suppressed the transcription of pgA, ltxA, and cdtB genes, which encode the poly-N-acetylglucosamine (PGA) polysaccharide of biofilm matrix and exotoxins leukotoxin and cytolethal distending toxin (CDT), respectively. The PLA produced by the MSC-C2 and K40 strains was increased several times by the addition of PPA to the MRS broth. The anti-biofilm effect of the extracts from the fermentation broth was proportional to the increasing PLA concentration, while a cumulatively higher effect than that of PLA alone suggested a combinational effect of PLA and the other metabolites, such as lactic acid (LA). Among the two medicinal plants, PLA, produced after the addition of PPA, was higher in PR extract in case of both the LAB strains. PLA production by the MSC-C2 strain in the PR extract reached 4.8 ± 0.23 mM, which was obviously higher than that in the MRS broth (3.88 ± 0.12 mM) supplemented with 1 mg/ml PPA. The activity to inhibit biofilm formation in the fermented PR extract was clearly high. PLA formed in the fermented PR extract downregulated the dispersin B encoding the dspB gene together with pgA, ltxA, and cdtB. In conclusion, this study shows a promising activity of PLA against the A. actinomycetemcomitans biofilm and virulence genes. In addition, the combinational effect of PLA and the medicinal plant extract can be achieved by fermentation with a specific plant-derived LAB strain.