Abstract

The global rise in antimicrobial resistance and lack of discovery of new antimicrobials have created serious concerns. Targeting quorum sensing (QS) and biofilms of pathogenic bacteria is considered a promising approach in antimicrobial drug discovery. This study explored the inhibitory effect of plumbagin against biofilms and QS of Chromobacterium violaceum, Serratia marcescens and Pseudomonas aeruginosa. Violacein production in C. violaceum 12472 was reduced by >80%. The virulent traits of P. aeruginosa PAO1 such as pyocyanin, rhamnolipid and proteases were also inhibited at sub-minimum inhibitory concentrations. Moreover, the biofilms of the test bacteria were reduced by 56–70%. Plumbagin reduced the bacterial adherence and colonization on solid surface. Computational studies gave closer insights regarding the possible modes of action. Molecular dynamics simulations revealed that the protein complexes were quite stable under physiological conditions. This study provides both experimental and computational evidence regarding the efficacy of plumbagin against biofilms and the QS-controlled virulence factors of Gram-negative bacteria.

摘要

全球抗微生物药物耐药性的上升和新抗微生物药物的发现不足已经引起了严重的关注。靶向群体感应（QS）和病原菌的生物膜被认为是抗菌药物发现的一种有前途的方法。本研究探讨了白花丹素对紫色色杆菌、粘质沙雷菌和铜绿假单胞菌的生物膜和QS的抑制作用。C. violaceum 12472 中的Violacein 产量减少了 >80%。铜绿假单胞菌的毒力性状PAO1，如绿脓素、鼠李糖脂和蛋白酶，在亚最低抑制浓度下也受到抑制。此外，测试细菌的生物膜减少了 56-70%。Plumbagin 减少了细菌在固体表面的粘附和定植。计算研究对可能的行动模式提供了更深入的见解。分子动力学模拟表明，蛋白质复合物在生理条件下非常稳定。这项研究提供了关于白花丹素对生物膜和革兰氏阴性菌的 QS 控制毒力因子的功效的实验和计算证据。