Pseudomonas aeruginosa quorum sensing and biofilm attenuation by a di-hydroxy derivative of piperlongumine (PL-18)

IF 5.9 Q1 MICROBIOLOGY Biofilm Pub Date : 2024-07-18 DOI:10.1016/j.bioflm.2024.100215

Yael Schlichter Kadosh , Subramani Muthuraman , Khairun Nisaa , Anat Ben-Zvi , Danit Lisa Karsagi Byron , Marilou Shagan , Alexander Brandis , Tevie Mehlman , Jacob Gopas , Rajendran Saravana Kumar , Ariel Kushmaro

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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.

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胡椒龙葵碱二羟基衍生物（PL-18）的铜绿假单胞菌法定人数感应和生物膜衰减作用

细菌通讯--定量感应（Quorum Sensing，QS）--是抑制毒力和预防抗生素耐药性感染的一个目标。研究人员筛选了 16 种胡椒龙舌兰碱（Piperlongumine，PL）的衍生物（一种来自胡椒龙舌兰的酰胺生物碱），以研究其对 QS 的抑制作用。PL-18 的 QSI 活性最佳。PL-18 可抑制铜绿假单胞菌的 lasR-lasI、rhlR-rhlI 和 pqs QS 系统。PL-18 可抑制作为 QS 控制毒力要素的焦花青素和鼠李糖脂。铁是致病性、生物膜形成和在恶劣环境中恢复能力的基本要素，PL-18 可抑制铁的吸收。PL-18 能明显减少生物膜的生物体积，包括已形成的生物膜。涂有 PL-18 的硅管明显抑制了生物膜的形成。对处理过的铜绿假单胞菌进行的转录组研究表明，PL-18 确实减少了 QS 和铁平衡相关基因的表达，并上调了硫代谢相关基因的表达。总之，PL-18 可抑制 QS、毒力、铁吸收和生物膜的形成。因此，应进一步开发 PL-18 来对抗细菌感染、抗生素耐药性和生物膜的形成。

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