title: 2,5-Piperazinedione inhibits quorum sensing-dependent factor production in Pseudomonas aeruginosa PAO1.
abstract: The effects of 2,5-piperazinedione in reducing the production of quorum sensing (QS)-dependent factors in Pseudomonas aeruginosa PAO1 were assessed both in vitro and in vivo. 2,5-Piperazinedione exhibited a 69% reduction in the azocasein-degrading proteolytic activity and a 48% reduction in the elastolytic activity of PAO1. Further, it showed 85% and 96% reduction in the production of pyocyanin and extracellular polymeric substances (EPS) of PAO1, respectively. In the swimming inhibition assay, 2,5-piperazinedione-treated PAO1 cells exhibited poor swimming motility in swim agar medium. In the in vivo analysis, an enhanced survival of PAO1-preinfected Caenorhabditis elegans was observed after treatment with 2,5-piperazinedione. Regarding the mode of action, in the molecular docking analysis, 2,5-piperazinedione interacts with the amino acid residue of the LasR receptor protein required for binding the natural ligand N -3-oxododecanoyl-l-homoserine lactone (3-oxo-C12-HSL). This demonstrates the probability of 2,5-piperazinedione to interfere with the binding process of 3-oxo-C12-HSL to its receptor protein. Thus, the findings of the present study reveal the potential of 2,5-piperazinedione in reducing the QS-dependent phenotypic features of PAO1.
authors.affiliation: Department of Biotechnology, Alagappa University, Karaikudi, Tamil Nadu, India.
authors.forename: Khadar Syed
authors.initials: KS
authors.lastname: Musthafa
authors.forename: Krishnaswamy
authors.initials: K
authors.lastname: Balamurugan
authors.forename: Shunmugiah Karutha
authors.initials: SK
authors.lastname: Pandian
authors.forename: Arumugam Veera
authors.initials: AV
authors.lastname: Ravi
mesh_terms: D015107:4-Butyrolactone / Q000031:analogs & derivatives / Q000378:metabolism; D000818:Animals; D001426:Bacterial Proteins / Q000037:antagonists & inhibitors* / Q000096:biosynthesis* / Q000378:metabolism; D017173:Caenorhabditis elegans / Q000187:drug effects / Q000382:microbiology; D006714:Homoserine / Q000031:analogs & derivatives / Q000378:metabolism; D010879:Piperazines / Q000494:pharmacology*; D011550:Pseudomonas aeruginosa / Q000187:drug effects* / Q000378:metabolism*; D011710:Pyocyanine / Q000096:biosynthesis / Q000378:metabolism; D053038:Quorum Sensing / Q000187:drug effects*; D012097:Repressor Proteins / Q000037:antagonists & inhibitors* / Q000096:biosynthesis* / Q000378:metabolism; D015534:Trans-Activators / Q000378:metabolism; D037521:Virulence Factors / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; C080365:LasR protein, Pseudomonas aeruginosa; C109860:N-(3-oxododecanoyl)homoserine lactone; D010879:Piperazines; C434259:QscR protein, Pseudomonas aeruginosa; D012097:Repressor Proteins; D015534:Trans-Activators; D037521:Virulence Factors; C003905:3,6-bis(5-chloro-2-piperidyl)-2,5-piperazinedione; D006714:Homoserine; D011710:Pyocyanine; D015107:4-Butyrolactone