Abstract

Quorum sensing (QS) enables virulence factors in bacteria for biofilm formation and pathogenic invasion. Therefore, quorum quenching (QQ), disruption of QS circuit, becomes an alternative antimicrobial therapy. In this study, leaf extract of Gynura procumbens (GP) was used to inhibit biofilm and virulent factors in Pseudomonas aeruginosa. The extract inhibited the biofilm production (p ≤ 0.05) in P. aeruginosa strains MZ2F and MZ4A. The minimum biofilm eradication concentration (MBEC) was recorded at 250 and 500 μg/ml while total activity was found at 288 and 144 ml/g, respectively. Moreover, a significant reduction of virulence factors (p ≤ 0.05) at sub-MBEC without affecting the growth implies the QQ action of the extract. The bioactive fractions were rich in polyphenols and tentatively identified as quercetin and myricetin (R_f=0.53-0.60). Furthermore, we employed computational methods to validate our findings and their interactions with QS receptors (LasR and RhlR). Interestingly, docking studies have also shown that quercetin and myricetin are the promising anti-QS agents out of 31 GP compounds. Notably, their binding affinity ranged between −9.77 and −10.52 kcal/mol for both QS receptors, with controls ranging from −5.40 to −8.97 kcal/mol. Besides, ΔG of quercetin and myricetin with LasR was −71.56 and −74.88 kcal/mol, respectively. Moreover, compounds were suitable drug candidates with stable binding interactions. Therefore, the anti-QS activity of GP leaves and the identified polyphenols can be used in developing QQ-based therapeutics.

Communicated by Ramaswamy H. Sarma

摘要

群体感应 (QS) 使细菌中的毒力因子能够形成生物膜和病原体入侵。因此，群体猝灭 (QQ)，即 QS 回路的中断，成为一种替代的抗菌疗法。在这项研究中，Gynura procumbens (GP) 的叶子提取物被用来抑制铜绿假单胞菌的生物膜和毒性因子。该提取物抑制铜绿假单胞菌菌株 MZ2F 和 MZ4A的生物膜生成 ( p ≤ 0.05 ) 。最低生物膜根除浓度 (MBEC) 记录为 250 和 500 μg/ml，而总活性分别为 288 和 144 ml/g。此外，毒力因子显着降低 ( p ≤ 0.05) 在亚 MBEC 下不影响生长意味着提取物的 QQ 作用。生物活性组分富含多酚，初步鉴定为槲皮素和杨梅素（R _f=0.53-0.60)。此外，我们采用计算方法来验证我们的发现及其与 QS 受体（LasR 和 RhlR）的相互作用。有趣的是，对接研究还表明，在 31 种 GP 化合物中，槲皮素和杨梅素是有前途的抗 QS 药物。值得注意的是，它们对两种 QS 受体的结合亲和力在 -9.77 和 -10.52 kcal/mol 之间，对照范围从 -5.40 到 -8.97 kcal/mol。此外，槲皮素和杨梅素与 LasR 的 ΔG 分别为 -71.56 和 -74.88 kcal/mol。此外，化合物是合适的候选药物，具有稳定的结合相互作用。因此，GP 叶子的抗 QS 活性和鉴定的多酚可用于开发基于 QQ 的疗法。

由 Ramaswamy H. Sarma 传达