title: A diketopiperazine factor from Rheinheimera aquimaris QSI02 exhibits anti-quorum sensing activity.
abstract: An ethyl acetate (EtOAc) extract isolated from the marine bacterium, Rheinheimera aquimaris QSI02, was found to exhibit anti-quorum sensing (anti-QS) activity. A subsequent bioassay-guided isolation protocol led to the detection of an active diketopiperazine factor, cyclo(Trp-Ser). Biosensor assay data showed that the minimum inhibitory concentration (MIC) of cyclo(Trp-Ser) ranged from 3.2 mg/ml to 6.4 mg/m for several microorganisms, including Escherichia coli, Chromobacterium violaceum CV026, Pseudomonas aeruginosa PA01, Staphylococcus aureus, and Candida albicans. Additionally, sub-MICs of cyclo(Trp-Ser) decreased the QS-regulated violacein production in C. violaceum CV026 by 67%. Furthermore, cyclo(Trp-Ser) can decrease QS-regulated pyocyanin production, elastase activity and biofilm formation in P. aeruginosa PA01 by 65%, 40% and 59.9%, respectively. Molecular docking results revealed that cyclo(Trp-Ser) binds to CviR receptor more rigidly than C6HSL with lower docking energy -8.68 kcal/mol, while with higher binding energy of -8.40 kcal/mol than 3-oxo-C12HSL in LasR receptor. Molecular dynamics simulation suggested that cyclo(Trp-Ser) is more easy to bind to CviR receptor than natural signaling molecule, but opposite in LasR receptor. These results suggest that cyclo(Trp-Ser) can be used as a potential inhibitor to control QS systems of C. violaceum and P. aeruginosa and provide increased the understanding of molecular mechanism that influences QS-regulated behaviors.
authors.affiliation: Center for Bioengineering and Biotechnology, China University of Petroleum (East China), Qingdao 266580, P. R. China.
authors.forename: Shiwei
authors.initials: S
authors.lastname: Sun
authors.affiliation: Center for Bioengineering and Biotechnology, China University of Petroleum (East China), Qingdao 266580, P. R. China.
authors.forename: Xiaoyun
authors.initials: X
authors.lastname: Dai
authors.affiliation: Center for Bioengineering and Biotechnology, China University of Petroleum (East China), Qingdao 266580, P. R. China.
authors.forename: Jiao
authors.initials: J
authors.lastname: Sun
authors.affiliation: Center for Bioengineering and Biotechnology, China University of Petroleum (East China), Qingdao 266580, P. R. China.
authors.forename: Xiangguo
authors.initials: X
authors.lastname: Bu
authors.affiliation: Center for Bioengineering and Biotechnology, China University of Petroleum (East China), Qingdao 266580, P. R. China.
authors.forename: Caihong
authors.initials: C
authors.lastname: Weng
authors.affiliation: Center for Bioengineering and Biotechnology, China University of Petroleum (East China), Qingdao 266580, P. R. China.
authors.forename: Hui
authors.initials: H
authors.lastname: Li
authors.affiliation: Center for Bioengineering and Biotechnology, China University of Petroleum (East China), Qingdao 266580, P. R. China.
authors.forename: Hu
authors.initials: H
authors.lastname: Zhu
mesh_terms: D000085:Acetates / Q000737:chemistry; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001422:Bacterial Adhesion / Q000187:drug effects; D018441:Biofilms / Q000187:drug effects; D001681:Biological Assay; D002176:Candida albicans / Q000187:drug effects; D002861:Chromobacterium / Q000187:drug effects; D054659:Diketopiperazines / Q000494:pharmacology*; D004926:Escherichia coli / Q000187:drug effects; D005285:Fermentation; D020563:Gammaproteobacteria / Q000737:chemistry*; D007211:Indoles / Q000737:chemistry; D008024:Ligands; D008826:Microbial Sensitivity Tests; D008968:Molecular Conformation; D062105:Molecular Docking Simulation; D011550:Pseudomonas aeruginosa / Q000187:drug effects; D011710:Pyocyanine / Q000737:chemistry; D053038:Quorum Sensing / Q000187:drug effects*; D013211:Staphylococcus aureus / Q000187:drug effects; D037521:Virulence Factors / Q000378:metabolism
chemical_list: D000085:Acetates; D000900:Anti-Bacterial Agents; D054659:Diketopiperazines; D007211:Indoles; D008024:Ligands; D037521:Virulence Factors; C007650:ethyl acetate; D011710:Pyocyanine; C063155:violacein