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(+)-萜品-4-醇通过上调种间群体感应信号二酮哌嗪和扩散信号因子来抑制生物膜的形成。

(+)-Terpinen-4-ol Inhibits Biofilm Formation by Upregulating the Interspecies Quorum Sensing Signals Diketopiperazines and Diffusing Signaling Factors.

机构信息

Department of Food Engineering, College of Biomass Science and Engineering, Sichuan University, Chengdu 610065, P. R. China.

Frontiers Science Center for Disease-related Molecular Network, Institutes for Systems Genetics, West China Hospital, Sichuan University, 88 Keyuan South Road, Hi-Tech Zone, Chengdu 610041, P. R. China.

出版信息

J Agric Food Chem. 2021 Mar 24;69(11):3496-3510. doi: 10.1021/acs.jafc.0c07826. Epub 2021 Mar 16.

DOI:10.1021/acs.jafc.0c07826
PMID:33724028
Abstract

is a Gram-positive endospore-forming foodborne pathogen that causes lethal food poisoning and significant economic losses, usually through biofilm- and endospore-induced recurrent cross- and postprocessing contamination. Due to the lack of critical inhibitory targets and control strategies, biofilm contamination is a problem that urgently needs a solution. In this study, the antibacterial and antibiofilm activities of several natural potential bacterial quorum sensing (QS) interferers, a group of spice-originated monoterpenoids, were screened, and terpinen-4-ol effectively inhibited growth and biofilm and spore germination with minimum growth inhibition and 50% biofilm inhibitory concentrations of 8 and 2 μmol/mL, respectively. FESEM/CLSM and phenotypic research illustrated that in addition to a decrease in the number of attached cells, (+)-terpinen-4-ol also obviously reduced extracellular matrix synthesis, especially exopolysaccharides, and inhibited the swarming motility and protease activity of . (+)-Terpinen-4-ol did not exert a significant effect on AI-2 signals in . Accordingly, the -produced interspecies QS signals diffusing signal factors (DSFs, C8-C15) and diketopiperazines (DKPs) were detected and identified here, which suppressed biofilm formation in a concentration-dependent manner. (+)-Terpinen-4-ol significantly increased the levels of specific DSF and DKP signals in and down-regulated the gene expression of some homologues in transcription level. Moreover, both DKPs and DSFs inhibited swarming motility and protease activity in , while just the DSF signals 2-dodecenoic acid and 11-methyl-2-dodecenoic acid inhibited exopolysaccharide synthesis like (+)-terpinen-4-ol. In summary, strains were found to produce nine DSF- and six DKP-type QS signaling molecules, which repressed biofilm formation. (+)-Terpinen-4-ol was confirmed to be a promising antibacterial and antibiofilm agent against upregulating DSFs and DKPs levels, and it could target the critical genes for DSFs turnover.

摘要

是一种革兰氏阳性产芽孢的食源性致病菌,可引起致命的食物中毒,并造成重大的经济损失,通常是通过生物膜和芽孢诱导的反复交叉和后处理污染造成的。由于缺乏关键的抑制靶点和控制策略,生物膜污染是一个亟待解决的问题。在这项研究中,筛选了几种天然潜在的细菌群体感应(QS)干扰物(一组源自香料的单萜)的抗菌和抗生物膜活性,萜品-4-醇有效地抑制了生长和生物膜,其最小生长抑制浓度和 50%生物膜抑制浓度分别为 8 和 2 μmol/mL。FESEM/CLSM 和表型研究表明,除了附着细胞数量减少外,(+)-萜品-4-醇还明显减少了细胞外基质的合成,特别是胞外多糖,并抑制了运动和蛋白酶活性。(+)-萜品-4-醇对 中 AI-2 信号没有显著影响。因此,在这里检测并鉴定了产生的种间 QS 信号扩散信号因子(DSFs,C8-C15)和二酮哌嗪(DKPs),它们以浓度依赖的方式抑制生物膜的形成。(+)-萜品-4-醇显著增加了 中特定 DSF 和 DKP 信号的水平,并在转录水平下调了一些 同源物的基因表达。此外,DKPs 和 DSFs 都抑制了 中的泳动运动和蛋白酶活性,而只有 DSF 信号 2-十二烯酸和 11-甲基-2-十二烯酸像(+)-萜品-4-醇一样抑制胞外多糖的合成。总之,发现 株产生九种 DSF 和六种 DKP 型 QS 信号分子,抑制生物膜形成。(+)-萜品-4-醇被证实是一种有前途的抗生物膜剂,可上调 DSFs 和 DKPs 水平,针对关键基因进行 DSFs 循环。

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