Department of Food Science and Technology, Pondicherry University, Puducherry 605014, India.
Centre for Bioinformatics, Pondicherry University, Puducherry 605014, India.
J Med Microbiol. 2020 Nov;69(11):1319-1331. doi: 10.1099/jmm.0.001261. Epub 2020 Oct 21.
is one of the leading food-borne entero-pathogens causing various illnesses ranging from gastroenteritis to systemic infections. Quorum sensing (QS) is one of the prime mechanisms that control the virulence in .. Vanillic acid inhibits the quorum sensing and other virulence factors related to . It has been evaluated by transcriptomic and Insilico analysis. Therefore, it can be a prospective agent to develop a therapeutic combination against . The present study is focused on screening natural anti-quorum-sensing agents against . The effect of selected active principle on various virulence factors was evaluated. In total, 12 phytochemicals were screened by swarming assay. MATH assay, EPS and surfactant production assay, SEM analysis, antibiotic and blood sensitivity assay were performed to demonstrate the anti-virulence activity. Further, RNA sequencing and molecular docking studies were carried out to substantiate the anti-QS activity. Vanillic acid (VA) has exhibited significant motility inhibition, thus indicating the anti-QS activity with MQIC of 400 µg ml without altering the cell viability. It has also inhibited the violacein production in ATCC 12472, which further confirms the anti-QS activity. VA has inhibited 16 % of cell-surface hydrophobicity (CSH), 52 % of EPS production and 60 % of surfactant production. Moreover, it has increased the sensitivity of towards antibiotics. It has also made the cells upto 91 % more vulnerable towards human immune cells. The transcriptomic analysis by RNA sequencing revealed the down regulation of genes related to motility, virulence, chemotaxis, siderophores and drug resistance. VA treatment has also positively regulated the expression of several stress response genes. In furtherance, the anti-QS potential of VA has been validated with QS regulatory protein YenR by molecular simulation and docking study. The present study is possibly the first attempt to demonstrate the anti-QS and anti-pathogenic potential of VA against by transcriptomic and analysis. It also deciphers that VA can be a promising lead to develop biopreservative and therapeutic regimens to treat infections.
是一种主要的食源性病原体，可引起从肠胃炎到全身感染等各种疾病。群体感应 (QS) 是控制 …… 毒力的主要机制之一。香草酸通过转录组学和 Insilico 分析来抑制群体感应和其他与 …… 相关的毒力因子。因此，它可以成为开发针对 …… 的治疗组合的有前途的药物。本研究集中于筛选针对 …… 的天然抗群体感应剂。评估了所选活性物质对各种毒力因子的影响。通过群体运动测定法筛选了 12 种植物化学物质。进行了 MATH 测定法、EPS 和表面活性剂产生测定法、SEM 分析、抗生素和血液敏感性测定法，以证明抗毒力活性。此外，进行了 RNA 测序和分子对接研究，以证实抗 QS 活性。香草酸 (VA) 表现出显著的运动抑制作用，因此表明 MQIC 为 400μg/ml 时具有抗 QS 活性，而不改变细胞活力。它还抑制了 ATCC 12472 中的紫质产生，这进一步证实了抗 QS 活性。VA 抑制了 16%的细胞表面疏水性 (CSH)、52%的 EPS 产生和 60%的表面活性剂产生。此外，它增加了对抗生素的敏感性。它还使细胞对人类免疫细胞的敏感性提高了 91%。通过 RNA 测序进行的转录组分析显示，与运动性、毒力、趋化性、铁载体和耐药性相关的基因下调。VA 处理还上调了几种应激反应基因的表达。此外，通过分子模拟和对接研究，用 QS 调节蛋白 YenR 验证了 VA 的抗 QS 潜力。本研究可能是首次尝试通过转录组学和分析来证明 VA 对 …… 的抗 QS 和抗致病潜力。它还揭示 VA 可以成为开发生物防腐剂和治疗方案来治疗 …… 感染的有前途的先导物。
