Biofilm (Dec 2024)

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

Journal volume & issue
Vol. 8
p. 100215

Abstract

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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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