title: Rule-based regulatory and metabolic model for Quorum sensing in P. aeruginosa.
abstract: BACKGROUND
  In the pathogen P. aeruginosa, the formation of virulence factors is regulated via Quorum sensing signaling pathways. Due to the increasing number of strains that are resistant to antibiotics, there is a high interest to develop novel antiinfectives. In the combat of resistant bacteria, selective blockade of the bacterial cell-to-cell communication (Quorum sensing) has gained special interest as anti-virulence strategy. Here, we modeled the las, rhl, and pqs Quorum sensing systems by a multi-level logical approach to analyze how enzyme inhibitors and receptor antagonists effect the formation of autoinducers and virulence factors.
  
  
  RESULTS
  Our rule-based simulations fulfill the behavior expected from literature considering the external level of autoinducers. In the presence of PqsBCD inhibitors, the external HHQ and PQS levels are indeed clearly reduced. The magnitude of this effect strongly depends on the inhibition level. However, it seems that the pyocyanin pathway is incomplete.
  
  
  CONCLUSIONS
  To match experimental observations we suggest a modified network topology in which PqsE and PqsR acts as receptors and an autoinducer as ligand that up-regulate pyocyanin in a concerted manner. While the PQS biosynthesis is more appropriate as target to inhibit the HHQ and PQS formation, blocking the receptor PqsR that regulates the biosynthesis reduces the pyocyanin level stronger.
authors: Center for Bioinformatics, Saarland University, Campus E2,1, 66123 Saarbrücken, Germany. volkhard.helms@bioinformatik.uni-saarland.de.
authors: Nadine S
authors: NS
authors: Schaadt
authors: Anke
authors: A
authors: Steinbach
authors: Rolf W
authors: RW
authors: Hartmann
authors: Volkhard
authors: V
authors: Helms
mesh_terms: D004791:Enzyme Inhibitors / Q000494:pharmacology; D053263:Gene Regulatory Networks / Q000187:drug effects; D006017:Glycolipids / Q000378:metabolism; D008954:Models, Biological; D011550:Pseudomonas aeruginosa / Q000166:cytology* / Q000235:genetics / Q000378:metabolism*; D011710:Pyocyanine / Q000378:metabolism; D053038:Quorum Sensing / Q000187:drug effects; D037521:Virulence Factors / Q000378:metabolism
chemical_list: D004791:Enzyme Inhibitors; D006017:Glycolipids; D037521:Virulence Factors; C418382:rhamnolipid; D011710:Pyocyanine
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