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
Affiliations
Yael Schlichter Kadosh
Avram and Stella Goldstein-Goren Department of Biotechnology Engineering, Ben Gurion University of the Negev, Beer Sheva, Israel
Subramani Muthuraman
Chemistry Division, Vellore Institute of Technology, Chennai, India
Khairun Nisaa
Department of Life Science, Ben-Gurion University of the Negev, Beer Sheva, Israel
Anat Ben-Zvi
Department of Life Science, Ben-Gurion University of the Negev, Beer Sheva, Israel
Danit Lisa Karsagi Byron
Department of Civil and Environmental Engineering, Ben-Gurion University of the Negev, Beer Sheva, Israel
Marilou Shagan
Avram and Stella Goldstein-Goren Department of Biotechnology Engineering, Ben Gurion University of the Negev, Beer Sheva, Israel
Alexander Brandis
Department of Life Sciences Core Facilities, Weizmann Institute of Science, Rehovot, Israel
Tevie Mehlman
Department of Life Sciences Core Facilities, Weizmann Institute of Science, Rehovot, Israel
Jacob Gopas
Department of Microbiology, Immunology and Genetics Faculty of Health Sciences, Ben Gurion University of the Negev, Beer Sheva, Israel
Rajendran Saravana Kumar
Chemistry Division, Vellore Institute of Technology, Chennai, India; Corresponding author.
Ariel Kushmaro
Avram and Stella Goldstein-Goren Department of Biotechnology Engineering, Ben Gurion University of the Negev, Beer Sheva, Israel; The Ilse Katz Center for Nanoscale Science and Technology, Ben Gurion University of the Negev, Beer Sheva, Israel; School of Sustainability and Climate Change, Ben Gurion University of the Negev, Beer Sheva, Israel; Corresponding author. Avram and Stella Goldstein-Goren Department of Biotechnology Engineering, Ben Gurion University of the Negev, Beer Sheva, Israel.
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.
