6-Gingerol reduces Pseudomonas aeruginosa biofilm formation and virulence via quorum sensing inhibition.
Pseudomonas aeruginosa is a well-known pathogenic bacterium that forms biofilms and produces virulence factors via quorum sensing (QS). Interfering with normal QS interactions between signal molecules and their cognate receptors is a developing strategy for attenuating its virulence. Here we tested the hypothesis that 6-gingerol, a pungent oil of fresh ginger, reduces biofilm formation and virulence by antagonistically binding to P. aeruginosa QS receptors. In silico studies demonstrated molecular binding occurs between 6-gingerol and the QS receptor LasR through hydrogen bonding and hydrophobic interactions. Experimentally 6-gingerol reduced biofilm formation, several virulence factors (e.g., exoprotease, rhamnolipid, and pyocyanin), and mice mortality. Further transcriptome analyses demonstrated that 6-gingerol successfully repressed QS-induced genes, specifically those related to the production of virulence factors. These results strongly support our hypothesis and offer insight into the molecular mechanism that caused QS gene repression.
School of Civil, Environmental and Architectural Engineering, Korea University, Anam-Dong, Seongbuk-Gu, Seoul 136-713, South Korea.
Han-Shin
HS
Kim
School of Civil, Environmental and Architectural Engineering, Korea University, Anam-Dong, Seongbuk-Gu, Seoul 136-713, South Korea.
Sang-Hoon
SH
Lee
College of Pharmacy, Korea University, Sejong-ro 2511, Jochiwon-eup, Sejong, 339-700, South Korea.
Youngjoo
Y
Byun
School of Civil, Environmental and Architectural Engineering, Korea University, Anam-Dong, Seongbuk-Gu, Seoul 136-713, South Korea.
Hee-Deung
HD
Park
D000818:Animals; D018441:Biofilms / Q000187:drug effects / Q000254:growth & development*; D002396:Catechols / Q000737:chemistry / Q000494:pharmacology*; D005233:Fatty Alcohols / Q000737:chemistry / Q000494:pharmacology*; D005260:Female; D020869:Gene Expression Profiling; D015964:Gene Expression Regulation, Bacterial / Q000187:drug effects; D008813:Mice, Inbred ICR; D062105:Molecular Docking Simulation; D011550:Pseudomonas aeruginosa / Q000187:drug effects / Q000235:genetics / Q000472:pathogenicity* / Q000502:physiology*; D053038:Quorum Sensing / Q000187:drug effects*; D014774:Virulence; D037521:Virulence Factors / Q000378:metabolism
D002396:Catechols; D005233:Fatty Alcohols; D037521:Virulence Factors; C007845:gingerol