TY - JOUR
T1 - Pseudomonas aeruginosa quorum sensing and biofilm attenuation by a di-hydroxy derivative of piperlongumine (PL-18)
AU - Schlichter Kadosh, Yael
AU - Muthuraman, Subramani
AU - Nisaa, Khairun
AU - Ben-Zvi, Anat
AU - Karsagi Byron, Danit Lisa
AU - Shagan, Marilou
AU - Brandis, Alexander
AU - Mehlman, Tevie
AU - Gopas, Jacob
AU - Saravana Kumar, Rajendran
AU - Kushmaro, Ariel
N1 - Publisher Copyright: © 2024 The Authors
PY - 2024/12/1
Y1 - 2024/12/1
N2 - 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.
AB - 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.
KW - Amide alkaloid
KW - Bacterial biofilm
KW - Iron acquisition
KW - Piper longum
KW - Piperlongumine
KW - Pseudomonas aeruginosa
KW - Quorum sensing
KW - Transcriptome
UR - http://www.scopus.com/inward/record.url?scp=85199387563&partnerID=8YFLogxK
U2 - 10.1016/j.bioflm.2024.100215
DO - 10.1016/j.bioflm.2024.100215
M3 - Article
C2 - 39148892
SN - 2590-2075
VL - 8
JO - Biofilm
JF - Biofilm
M1 - 100215
ER -