Bicyclic brominated furanones: a new class of quorum sensing modulators that inhibit bacterial biofilm formation.
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.
Department of Chemistry, Syracuse University, Syracuse, NY 13244, United States.
Sijie
S
Yang
Department of Surgery, Upstate Medical University, State University of New York, Syracuse, NY 13210, United States.
Osama A
OA
Abdel-Razek
Department of Chemistry, Syracuse University, Syracuse, NY 13244, United States.
Fei
F
Cheng
Department of Chemistry, Syracuse University, Syracuse, NY 13244, United States.
Debjyoti
D
Bandyopadhyay
Department of Chemistry, Syracuse University, Syracuse, NY 13244, United States.
Gauri S
GS
Shetye
Department of Surgery, Upstate Medical University, State University of New York, Syracuse, NY 13210, United States.
Guirong
G
Wang
Department of Chemistry, Syracuse University, Syracuse, NY 13244, United States; Department of Biomedical and Chemical Engineering, Syracuse University, Syracuse, NY 13244, United States. Electronic address: yluk@syr.edu.
Yan-Yeung
YY
Luk
D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D018441:Biofilms / Q000187:drug effects*; D001643:Bridged Bicyclo Compounds / Q000737:chemistry*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D005663:Furans / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D054879:Halogenation; D006801:Humans; D011550:Pseudomonas aeruginosa / Q000187:drug effects / Q000502:physiology*; D053038:Quorum Sensing / Q000187:drug effects
D000900:Anti-Bacterial Agents; D001643:Bridged Bicyclo Compounds; D005663:Furans
Biofilm inhibition; Cell signaling; Furanones; Toxicity; Virulence factor