TY - JOUR
T1 - Bicyclic brominated furanones
T2 - A new class of quorum sensing modulators that inhibit bacterial biofilm formation
AU - Yang, Sijie
AU - Abdel-Razek, Osama A.
AU - Cheng, Fei
AU - Bandyopadhyay, Debjyoti
AU - Shetye, Gauri S.
AU - Wang, Guirong
AU - Luk, Yan Yeung
N1 - Funding Information:
This work was partially supported by NSF-CAREER ( #0845686 , PI Y.Y.L), NSF-EFRI ( #1137186 , coPI, Y.Y.L), and NIH HL096007 (G.W.). We thank Bonnie B. Toms (Upstate Medical University, SUNY) for the generous donation of human neuroblastoma cell line SK-N-SH. We thank Dr. Helen E. Blackwell (Univ. of Wisconsin-Madison) for the generous donation of strains PAO-JP2 (p lasI -LVAgfp) and PAO-JP2 (p rhlI -LVAgfp), Dr. Dacheng Ren (SU) for the generous donation of strains E. coli RP437, E. coli RP437(pRSH103), and Dr. Hiroaki Suga (The University of Tokyo) for the generous donation of plasmids p lasI -LVAgfp and p rhlI -LVAgfp. We also thank Dr. James L. Hougland (SU) for the use of fluorescence plate reader and the review of the manuscript.
PY - 2014/2/15
Y1 - 2014/2/15
N2 - Both natural and synthetic brominated furanones are known to inhibit biofilm formation by bacteria, but their toxicity to mammalian cells is often not reported. Here, we designed and synthesized a new class of brominated furanones (BBFs) that contained a bicyclic structure having one bromide group with well-defined regiochemistry. This class of molecules exhibited reduction in the toxicity to mammalian cells (human neuroblastoma SK-N-SH) and did not inhibit bacteria (Pseudomonas aeruginosa and Escherichia coli) growth, but retained the inhibitory activity towards biofilm formation of bacteria. In addition, all the BBFs inhibited the production of virulence factor elastase B in P. aeruginosa. To explore the effect of BBFs on quorum sensing, we used a reporter gene assay and found that 6-BBF and 7-BBF exhibited antagonistic activities for LasR protein in the lasI quorum sensing circuit, while 5-BBF showed agonistic activity for the rhlI quorum sensing circuit. This study suggests that structural variation of brominated furanones can be designed for targeted functions to control biofilm formation.
AB - Both natural and synthetic brominated furanones are known to inhibit biofilm formation by bacteria, but their toxicity to mammalian cells is often not reported. Here, we designed and synthesized a new class of brominated furanones (BBFs) that contained a bicyclic structure having one bromide group with well-defined regiochemistry. This class of molecules exhibited reduction in the toxicity to mammalian cells (human neuroblastoma SK-N-SH) and did not inhibit bacteria (Pseudomonas aeruginosa and Escherichia coli) growth, but retained the inhibitory activity towards biofilm formation of bacteria. In addition, all the BBFs inhibited the production of virulence factor elastase B in P. aeruginosa. To explore the effect of BBFs on quorum sensing, we used a reporter gene assay and found that 6-BBF and 7-BBF exhibited antagonistic activities for LasR protein in the lasI quorum sensing circuit, while 5-BBF showed agonistic activity for the rhlI quorum sensing circuit. This study suggests that structural variation of brominated furanones can be designed for targeted functions to control biofilm formation.
KW - Biofilm inhibition
KW - Cell signaling
KW - Furanones
KW - Toxicity
KW - Virulence factor
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U2 - 10.1016/j.bmc.2014.01.004
DO - 10.1016/j.bmc.2014.01.004
M3 - Article
C2 - 24485124
AN - SCOPUS:84893784979
SN - 0968-0896
VL - 22
SP - 1313
EP - 1317
JO - Bioorganic and Medicinal Chemistry
JF - Bioorganic and Medicinal Chemistry
IS - 4
ER -