PDF(Pubmed)
Abstract：
Bacterial communication, Quorum Sensing (QS), is a target against virulence and prevention of antibiotic-resistant infections. 16 derivatives of Piperlongumine (PL), an amide alkaloid from Piper longum L., were screened for QS inhibition. PL-18 had the best QSI activity. PL-18 inhibited the lasR-lasI, rhlR-rhlI, and pqs QS systems of Pseudomonas aeruginosa. PL-18 inhibited pyocyanin and rhamnolipids that are QS-controlled virulence elements. Iron is an essential element for pathogenicity, biofilm formation and resilience in harsh environments, its uptake was inhibited by PL-18. Pl-18 significantly reduced the biofilm biovolume including in established biofilms. PL-18-coated silicon tubes significantly inhibited biofilm formation. The transcriptome study of treated P. aeruginosa showed that PL-18 indeed reduced the expression of QS and iron homeostasis related genes, and up regulated sulfur metabolism related genes. Altogether, PL-18 inhibits QS, virulence, iron uptake, and biofilm formation. Thus, PL-18 should be further developed against bacterial infection, antibiotic resistance, and biofilm formation.
摘要：
细菌通讯,QuorumSensing(QS),是对抗毒力和预防抗生素耐药性感染的目标。16衍生物的胡椒长胺（PL），一种来自PiperlongumL.的酰胺生物碱，对QS抑制进行筛选。PL-18具有最好的QSI活性。PL-18抑制了lasR-lasI,rhlR-rhlI,铜绿假单胞菌的pqsQS系统。PL-18抑制作为QS控制的毒力元件的绿脓苷和鼠李糖脂。铁是致病性的基本要素，在恶劣环境中形成生物膜和恢复能力，其摄取被PL-18抑制。Pl-18显著减少生物膜生物体积,包括在已建立的生物膜中。PL-18涂覆的硅管显著抑制生物膜形成。经过处理的铜绿假单胞菌的转录组研究表明，PL-18确实降低了QS和铁稳态相关基因的表达，并上调硫代谢相关基因。总之,PL-18抑制QS，毒力,铁吸收，和生物膜的形成。因此，PL-18应该进一步开发针对细菌感染，抗生素耐药性,和生物膜的形成。
