title: Cis-2-dodecenoic acid signal modulates virulence of Pseudomonas aeruginosa through interference with quorum sensing systems and T3SS.
abstract: BACKGROUND
  Cis-2-dodecenoic acid (BDSF) is well known for its important functions in intraspecies signaling in Burkholderia cenocepacia. Previous work has also established an important role of BDSF in interspecies and inter-kingdom communications. It was identified that BDSF modulates virulence of Pseudomonas aeruginosa. However, how BDSF interferes with virulence of P. aeruginosa is still not clear.
  
  
  RESULTS
  We report here that BDSF mediates the cross-talk between B. cenocepacia and P. aeruginosa through interference with quorum sensing (QS) systems and type III secretion system (T3SS) of P. aeruginosa. Bioassay results revealed that exogenous addition of BDSF not only reduced the transcriptional expression of the regulator encoding gene of QS systems, i.e., lasR, pqsR, and rhlR, but also simultaneously decreased the production of QS signals including 3-oxo-C12-HSL, Pseudomonas quinolone signal (PQS) and C4-HSL, consequently resulting in the down-regulation of biofilm formation and virulence factor production of P. aeruginosa. Furthermore, BDSF and some of its derivatives are also capable of inhibiting T3SS of P. aeruginosa at a micromolar level. Treatment with BDSF obviously reduced the virulence of P. aeruginosa in both HeLa cell and zebrafish infection models.
  
  
  CONCLUSIONS
  These results depict that BDSF modulates virulence of P. aeruginosa through interference with QS systems and T3SS.
authors.affiliation: Institute of Molecular and Cell Biology, Proteos, 61 Biopolis Drive, Singapore, 138673, Singapore. ydeng@imcb.a-star.edu.sg.
authors.forename: Yinyue
authors.initials: Y
authors.lastname: Deng
authors.forename: Calvin
authors.initials: C
authors.lastname: Boon
authors.forename: Shaohua
authors.initials: S
authors.lastname: Chen
authors.forename: Amy
authors.initials: A
authors.lastname: Lim
authors.forename: Lian-Hui
authors.initials: LH
authors.lastname: Zhang
mesh_terms: D015107:4-Butyrolactone / Q000031:analogs & derivatives / Q000378:metabolism; D000818:Animals; D000898:Antibiosis; D058947:Bacterial Secretion Systems / Q000187:drug effects; D018441:Biofilms / Q000254:growth & development; D057508:Burkholderia cenocepacia / Q000378:metabolism*; D004195:Disease Models, Animal; D004847:Epithelial Cells / Q000382:microbiology; D005229:Fatty Acids, Monounsaturated / Q000378:metabolism*; D020869:Gene Expression Profiling; D006367:HeLa Cells; D006714:Homoserine / Q000031:analogs & derivatives / Q000378:metabolism; D006801:Humans; D011552:Pseudomonas Infections / Q000382:microbiology / Q000473:pathology; D011550:Pseudomonas aeruginosa / Q000378:metabolism* / Q000472:pathogenicity* / Q000502:physiology; D015363:Quinolones / Q000378:metabolism; D053038:Quorum Sensing; D015398:Signal Transduction; D014774:Virulence; D037521:Virulence Factors / Q000096:biosynthesis; D015027:Zebrafish
chemical_list: C527562:2-dodecenoic acid; C407944:2-heptyl-3-hydroxy-4-quinolone; D058947:Bacterial Secretion Systems; D005229:Fatty Acids, Monounsaturated; C109860:N-(3-oxododecanoyl)homoserine lactone; C092312:N-butyrylhomoserine lactone; D015363:Quinolones; D037521:Virulence Factors; D006714:Homoserine; D015107:4-Butyrolactone