@phdthesis{1197504,
  abstract     = {{Antibiotic resistance in bacteria is a growing problem and innovative antimicrobials with novel targets and modes of action are needed. Bacteria use communication systems (quorum sensing; QS) for the coordination of virulence expression and biofilm formation and/or maturation so QS is an attractive target for novel anti-infective agents. It was our goal to implement and optimize different biosensors for the detection of QS inhibition and to investigate the antibiofilm effect of established and new QS inhibitors (QSI). QS inhibition was observed in different biosensors and several QSI affected later stages of biofilm development/maturation and/or promoted detachment. We observed that QSI increased the susceptibility of bacterial biofilms towards conventional antibiotics, indicating that a combined treatment could be useful. In addition, this could broaden the therapeutic choice since antibiotics which have become ineffective could possibly regain efficacy when used in combination with QSI. Several new QSI were also discovered. An adenosine derivative with a p-methoxyphenylpropionamide moiety at C-3’ and an analog lacking the adenine base inhibited the AI-2 QS system by interfering with LuxPQ. In a parallel study we discovered that cinnamaldehyde derivatives inhibited AI-2 QS by decreasing the DNA binding ability of LuxR. An α,β unsaturated side chain capable of reacting through Michael-addition, a hydrophobic moiety as well as a (partially) negative charge were necessary for this activity. In addition, QSI reduced in vitro virulence factor production and in vivo virulence of several Vibrio spp. 
In conclusion, we have elucidated the mechanism of action of established QSI and have discovered novel QSI. We have shown that these compounds affect virulence factor production and biofilm formation in several pathogenic bacteria and have provided evidence that QSI could contribute to the control of bacterial infections, either alone or in combination with antibiotics.}},
  author       = {{Brackman, Gilles}},
  keywords     = {{ANTIBIOTICS,BIOFILM,QUORUM SENSING}},
  language     = {{eng}},
  pages        = {{284}},
  publisher    = {{Ghent University. Faculty of Pharmaceutical Sciences}},
  school       = {{Ghent University}},
  title        = {{Interfering with quorum sensing as a novel strategy to combat bacterial infections}},
  year         = {{2011}},
}