Furanone derivatives as quorum-sensing antagonists of Pseudomonas aeruginosa.
The biofilm formation of Pseudomonas aeruginosa, an opportunistic human pathogen, is developed by cell-to-cell signaling, so-called quorum sensing (QS). To control the biofilm formation, we designed and synthesized new QS inhibitors of P. aeruginosa based on the structure of the previously known QS inhibitor, furanone. Newly synthesized compounds were a series of analogs of (5-oxo-2,5-dihydrofuran-3-yl)methyl alkanoate, and the structures of all six synthesized compounds was confirmed by NMR and GC/MS analyses. These new QS inhibitor candidates could remarkably inhibit both Pseudomonas QS signaling and biofilm formation, which were assayed by using the recombinant reporter system and flow cell confocal microscopy. The degree of QS inhibition by these new inhibitors varied from 20% to 90%. For the profound understanding about inhibition mechanism, we tried to estimate the binding energy between QS receptor, LasR, and our inhibitors from the in silico modeling system. The predicted binding pattern from the modeling system and our experimental data about QS inhibition were in good agreement. From these results, we suggest a new approach to develop the QS inhibitors and biofilm control agents based on structural modeling.
School of Chemical and Biological Engineering, Seoul National University, San 56-1, Sillim-dong, Gwanak-gu, Seoul, South Korea.
Cheoljin
C
Kim
Jaeeun
J
Kim
Hyung-Yeon
HY
Park
Hee-Jin
HJ
Park
Joon Hee
JH
Lee
Chan Kyung
CK
Kim
Jeyong
J
Yoon
D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D018441:Biofilms / Q000187:drug effects; D015195:Drug Design; D005663:Furans / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011485:Protein Binding; D011550:Pseudomonas aeruginosa / Q000737:chemistry / Q000187:drug effects* / Q000235:genetics / Q000502:physiology*; D053038:Quorum Sensing / Q000187:drug effects*; D016415:Sequence Alignment; D015534:Trans-Activators / Q000737:chemistry / Q000235:genetics / Q000378:metabolism
D001426:Bacterial Proteins; D005663:Furans; C080365:LasR protein, Pseudomonas aeruginosa; D015534:Trans-Activators