Department of Chemistry, Faculty of Sciences, University of Zanjan, 45371-38791, Zanjan, IR, Iran.
Department of Chemistry, Faculty of Sciences, University of Zanjan, 45371-38791, Zanjan, IR, Iran.
Microb Pathog. 2017 Nov;112:103-110. doi: 10.1016/j.micpath.2017.09.043. Epub 2017 Sep 20.
Pseudomonas aeruginosa quorum sensing (QS) system is a cell to cell signaling mechanism that regulates virulence factors and pathogenicity. Therefore, the QS system in P. aeruginosa may be an important target for pharmacological intervention. The present study aimed to investigate the effects of sub-MIC concentrations of (S,E)-2-hydroxy-N-(3-hydroxy-5-(hydroxymethyl)-2-methylpyridin-4-yl)propane hydrazide (pyridoxal lactohydrazone) against P. aeruginosa QS related virulence factors. We investigated the effect of sub-MIC concentrations of chiral pyridoxal lactohydrazone, which formed by the reaction of chiral lactic acid hydrazide and pyridoxal (one form of Vitamin B6) as bioactive reagents, on virulence factors. Treated PAO1 cultures in the presence of tested compound at 1/4 and 1/16 MIC (32 and 8 μg/mL respectively) showed significant inhibition of virulence factors including motility, alginate and pyocyanin production and susceptibility to HO (P < 0.001). Also, the pyridoxal lactohydrazone showed anti-QS activity in Chromobacterium violaceum CV026 biosensor bioassay. Because of quorum sensing is a promising target for anti-virulence therapy and also important role of LasR regulatory protein in the initiation of P. aeruginosa QS system, we carried out molecular docking for understanding the interactions of pyridoxal lactohydrazone with the LasR receptor. The results of docking study suggested that the pyridoxal lactohydrazone has potential to inhibit the LasR protein. The results indicated that sub-MIC concentrations of this compound exhibited inhibitory effect on P. aeruginosa QS related virulence factors.
铜绿假单胞菌群体感应（QS）系统是一种细胞间信号机制，调节毒力因子和致病性。因此，铜绿假单胞菌中的 QS 系统可能是药物干预的重要靶点。本研究旨在探讨亚最小抑菌浓度（sub-MIC）浓度的（S，E）-2-羟基-N-（3-羟基-5-（羟甲基）-2-甲基吡啶-4-基）丙烷酰肼（吡哆醛乳糖肼）对铜绿假单胞菌 QS 相关毒力因子的影响。我们研究了手性吡哆醛乳糖肼在亚 MIC 浓度下的作用，该化合物是由手性乳酸肼和吡哆醛（维生素 B6 的一种形式）反应形成的生物活性试剂，对毒力因子的影响。在测试化合物存在下，PAO1 培养物在 1/4 和 1/16 MIC（分别为 32 和 8μg/ml）下处理显示出对毒力因子（包括运动性、藻酸盐和绿脓菌素产生以及对 HO 的敏感性）的显著抑制（P<0.001）。此外，吡哆醛乳糖肼在 Chromobacterium violaceum CV026 生物传感器生物测定中显示出抗 QS 活性。由于群体感应是抗毒力治疗的一个有前途的靶点，而且 LasR 调节蛋白在铜绿假单胞菌 QS 系统的启动中也起着重要作用，我们进行了分子对接，以了解吡哆醛乳糖肼与 LasR 受体的相互作用。对接研究的结果表明，吡哆醛乳糖肼有可能抑制 LasR 蛋白。结果表明，该化合物的亚 MIC 浓度对铜绿假单胞菌 QS 相关毒力因子表现出抑制作用。
