title: Plakofuranolactone as a Quorum Quenching Agent from the Indonesian Sponge Plakortis cf. lita.
abstract: There is an urgent need for novel strategies to fight drug resistance and multi-drug resistance. As an alternative to the classic antibiotic therapy, attenuation of the bacteria virulence affecting their Quorum sensing (QS) system is a promising approach. Quorum sensing (QS) is a genetic regulation system that allows bacteria to communicate with each other and coordinate group behaviors. A new γ-lactone that is capable of inhibiting the LasI/R QS system, plakofuranolactone (1), was discovered in the extract of the marine spongePlakortiscf.lita, and its structure, including absolute configuration, was determined by NMR spectroscopy, MS spectrometry, and quantum-mechanical prediction of optical rotation. The quorum quenching activity of plakofuranolactone was evaluated using reporter gene assays for long- and short-chain signals (E. colipSB1075,E. colipSB401, andC. violeaceumCV026) and was confirmed by measuring the total protease activity (a virulence factor which is under control of the LasI/R system) of the wild-typeP. aeruginosaPAO1. Further research will be pursued to assess the potential of plakofuranolactone as a new antivirulence lead compound and a chemical tool to increase the knowledge in this field.
authors.affiliation: The Blue Chemistry Lab Group, Department of Pharmacy, University of Naples Federico II, 80131 Napoli, Italy. valeria.costantino@unina.it.
authors.forename: Valeria
authors.initials: V
authors.lastname: Costantino
authors.affiliation: The Blue Chemistry Lab Group, Department of Pharmacy, University of Naples Federico II, 80131 Napoli, Italy. gerardo.dellasala@unina.it.
authors.forename: Gerardo
authors.initials: G
authors.lastname: Della Sala
authors.affiliation: Department of Marine Biology, Leon H. Charney School of Marine Sciences, University of Haifa, Mt. Carmel, 31905 Haifa, Israel. sauravverma17@gmail.com.
authors.forename: Kumar
authors.initials: K
authors.lastname: Saurav
authors.affiliation: The Blue Chemistry Lab Group, Department of Pharmacy, University of Naples Federico II, 80131 Napoli, Italy. roberta.teta@unina.it.
authors.forename: Roberta
authors.initials: R
authors.lastname: Teta
authors.affiliation: Department of Marine Biology, Leon H. Charney School of Marine Sciences, University of Haifa, Mt. Carmel, 31905 Haifa, Israel. rbar-shal@univ.haifa.ac.il.
authors.forename: Rinat
authors.initials: R
authors.lastname: Bar-Shalom
authors.affiliation: The Blue Chemistry Lab Group, Department of Pharmacy, University of Naples Federico II, 80131 Napoli, Italy. alfonso.mangoni@unina.it.
authors.forename: Alfonso
authors.initials: A
authors.lastname: Mangoni
authors.affiliation: Department of Marine Biology, Leon H. Charney School of Marine Sciences, University of Haifa, Mt. Carmel, 31905 Haifa, Israel. lsteindler@univ.haifa.ac.il.
authors.forename: Laura
authors.initials: L
authors.lastname: Steindler
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology; D000890:Anti-Infective Agents / Q000737:chemistry* / Q000494:pharmacology; D001419:Bacteria / Q000187:drug effects; D018432:Drug Resistance, Multiple / Q000187:drug effects; D004926:Escherichia coli / Q000378:metabolism; D007214:Indonesia; D047229:Plakortis / Q000737:chemistry*; D011161:Porifera / Q000737:chemistry*; D053038:Quorum Sensing / Q000187:drug effects*; D014774:Virulence / Q000187:drug effects; D037521:Virulence Factors / Q000378:metabolism
chemical_list: D000900:Anti-Bacterial Agents; D000890:Anti-Infective Agents; D037521:Virulence Factors
keywords: Plakortis lita; Pseudomonas aeruginosa; antibacterial from marine sponges; antivirulence lead compounds; marine sponges; plakofuranolactone; quorum quenching activity; quorum sensing system; reporter gene assays