title: Effects of natural and chemically synthesized furanones on quorum sensing in Chromobacterium violaceum.
abstract: BACKGROUND
  Cell to cell signaling systems in Gram-negative bacteria rely on small diffusible molecules such as the N-acylhomoserine lactones (AHL). These compounds are involved in the production of antibiotics, exoenzymes, virulence factors and biofilm formation. They belong to the class of furanone derivatives which are frequently found in nature as pheromones, flavor compounds or secondary metabolites. To obtain more information on the relation between molecular structure and quorum sensing, we tested a variety of natural and chemically synthesized furanones for their ability to interfere with the quorum sensing mechanism using a quantitative bioassay with Chromobacterium violaceum CV026 for antagonistic and agonistic action. We were looking at the following questions: 1) Do these compounds affect growth? 2) Do these compounds activate the quorum sensing system of C. violaceum CV026? 3) Do these compounds inhibit violacein formation induced by the addition of the natural inducer N-hexanoylhomoserine lactone (HHL)? 4) Do these compounds enhance violacein formation in presence of HHL?
  
  
  RESULTS
  The naturally produced N-acylhomoserine lactones showed a strong non-linear concentration dependent influence on violacein production in C. violaceum with a maximum at 3.7*10-8 M with HHL. Apart from the N-acylhomoserine lactones only one furanone (emoxyfurane) was found to simulate N-acylhomoserine lactone activity and induce violacein formation. The most effective substances acting negatively both on growth and quorum sensing were analogs and intermediates in synthesis of the butenolides from Streptomyces antibioticus.
  
  
  CONCLUSIONS
  As the regulation of many bacterial processes is governed by quorum sensing systems, the finding of natural and synthetic furanones acting as agonists or antagonists suggests an interesting tool to control and handle detrimental AHL induced effects. Some effects are due to general toxicity; others are explained by a competitive interaction for LuxR proteins. For further experiments it is important to be aware of the fact that quorum sensing active compounds have non-linear effects. Inducers can act as inhibitors and inhibitors might be able to activate or enhance the quorum sensing system depending on chemical structure and concentration levels.
authors.affiliation: University of Zurich, Institut für Umweltwissenschaften, Winterthurerstrasse 190, 8057 Zurich, Switzerland. daniel@martinelli.com
authors.forename: Daniel
authors.initials: D
authors.lastname: Martinelli
authors.forename: Gilles
authors.initials: G
authors.lastname: Grossmann
authors.forename: Urs
authors.initials: U
authors.lastname: Séquin
authors.forename: Helmut
authors.initials: H
authors.lastname: Brandl
authors.forename: Reinhard
authors.initials: R
authors.lastname: Bachofen
mesh_terms: D015107:4-Butyrolactone / Q000031:analogs & derivatives* / Q000494:pharmacology; D002861:Chromobacterium / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism / Q000502:physiology*; D005663:Furans / Q000494:pharmacology*; D007211:Indoles / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D013329:Structure-Activity Relationship
chemical_list: D005663:Furans; D007211:Indoles; C104908:N-hexanoyl-L-homoserine lactone; C088386:homoserine lactone; D015107:4-Butyrolactone; C063155:violacein