Bicyclic brominated furanones: A new class of quorum sensing modulators that inhibit bacterial biofilm formation |
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| Institution: | 1. Department of Chemistry, Syracuse University, Syracuse, NY 13244, United States;2. Department of Surgery, Upstate Medical University, State University of New York, Syracuse, NY 13210, United States;3. Department of Biomedical and Chemical Engineering, Syracuse University, Syracuse, NY 13244, United States;1. Faculté de Pharmacie, Laboratoire de Pharmacologie Marine, 5000 Monastir, Tunisia;2. Torrey Pines Institute for Molecular Studies, Port Saint Lucie, FL 34987, United States;3. Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, UK;1. Department of Chemistry, Rhodes University, Grahamstown 6140, South Africa;2. Department of Biochemistry and Microbiolgy, Rhodes University, Grahamstown 6140, South Africa;3. Centre for Chemico- and Biomedicinal Research, Rhodes University, Grahamstown 6140, South Africa |
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| Abstract: | 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. |
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| Keywords: | Furanones Biofilm inhibition Virulence factor Cell signaling Toxicity |
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