title: Dissecting AI-2-mediated quorum sensing through C5-analogue synthesis and biochemical analysis.
abstract: Autoinducer-2 (AI-2)-mediated quorum sensing (QS) is utilised for both intra- and inter-species communication by a wide variety of bacteria. An understanding of the mechanism of this communication has the potential to elucidate new targets for antibacterial therapeutics. Herein, we report the synthesis of DPD analogues with modified dynamic equilibria and the evaluation of their behaviour in Gram-negative bacteria. None of the compounds showed modulation of QS inS.Typhimurium, and although no antagonism ofV. harveyiwas observed, chloro-analogueC5-Cl-DPDshowed modest agonism in this marine bacterium. This raises the possibility that access to a cyclic form of DPD may not be required for AI-2-mediated QS inV. harveyi.
authors.affiliation: Departments of Chemistry and Immunology, The Skaggs Institute for Chemical Biology, Worm Institute of Research and Medicine (WIRM), The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, United States.
authors.forename: Karen C
authors.initials: KC
authors.lastname: Collins
authors.affiliation: Departments of Chemistry and Immunology, The Skaggs Institute for Chemical Biology, Worm Institute of Research and Medicine (WIRM), The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, United States.
authors.forename: Kyoji
authors.initials: K
authors.lastname: Tsuchikama
authors.affiliation: Departments of Chemistry and Immunology, The Skaggs Institute for Chemical Biology, Worm Institute of Research and Medicine (WIRM), The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, United States.
authors.forename: Colin A
authors.initials: CA
authors.lastname: Lowery
authors.affiliation: Departments of Chemistry and Immunology, The Skaggs Institute for Chemical Biology, Worm Institute of Research and Medicine (WIRM), The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, United States.
authors.forename: Jie
authors.initials: J
authors.lastname: Zhu
authors.affiliation: Departments of Chemistry and Immunology, The Skaggs Institute for Chemical Biology, Worm Institute of Research and Medicine (WIRM), The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, United States.
authors.forename: Kim D
authors.initials: KD
authors.lastname: Janda