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

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

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

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.

Original languageEnglish
Article number100215
JournalBiofilm
Volume8
DOIs
StatePublished - 1 Dec 2024

Keywords

  • Amide alkaloid
  • Bacterial biofilm
  • Iron acquisition
  • Piper longum
  • Piperlongumine
  • Pseudomonas aeruginosa
  • Quorum sensing
  • Transcriptome

ASJC Scopus subject areas

  • Microbiology
  • Applied Microbiology and Biotechnology
  • Molecular Biology
  • Cell Biology

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