title: Stereochemical diversity of AI-2 analogs modulates quorum sensing in Vibrio harveyi and Escherichia coli.
abstract: Bacteria coordinate population-dependent behaviors such as virulence by intra- and inter-species communication (quorum sensing). Autoinducer-2 (AI-2) regulates inter-species quorum sensing. AI-2 derives from the spontaneous cyclisation of linear (S)-4,5-dihydroxypentanedione (DPD) into two isomeric forms in dynamic equilibrium. Different species of bacteria have different classes of AI-2 receptors (LsrB and LuxP) which bind to different cyclic forms. In the present work, DPD analogs with a new stereocenter at C-5 (4,5-dihydroxyhexanediones (DHDs)) have been synthesized and their biological activity tested in two bacteria. (4S,5R)-DHD is a synergistic agonist in Escherichia coli (which contains the LsrB receptor), while it is an agonist in Vibrio harveyi (LuxP), displaying the strongest agonistic activity reported so far (EC(50)=0.65μM) in this organism. Thus, modification at C-5 opens the way to novel methods to manipulate quorum sensing as a method for controlling bacteria.
authors.affiliation: Instituto de Tecnologia Química e Biológica, Av. da República, Estação Agronómica Nacional, 2780-157 Oeiras, Portugal.
authors.forename: Fabio
authors.initials: F
authors.lastname: Rui
authors.forename: João C
authors.initials: JC
authors.lastname: Marques
authors.forename: Stephen T
authors.initials: ST
authors.lastname: Miller
authors.forename: Christopher D
authors.initials: CD
authors.lastname: Maycock
authors.forename: Karina B
authors.initials: KB
authors.lastname: Xavier
authors.forename: M Rita
authors.initials: MR
authors.lastname: Ventura
mesh_terms: D001426:Bacterial Proteins / Q000819:agonists / Q000378:metabolism; D003500:Cyclization; D004926:Escherichia coli / Q000187:drug effects* / Q000378:metabolism*; D029968:Escherichia coli Proteins / Q000819:agonists / Q000378:metabolism; D006586:Hexanes / Q000737:chemistry; D006714:Homoserine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D007783:Lactones / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D010420:Pentanes / Q000737:chemistry; D053038:Quorum Sensing / Q000187:drug effects*; D012097:Repressor Proteins / Q000819:agonists / Q000378:metabolism; D013237:Stereoisomerism; D014733:Vibrio / Q000187:drug effects* / Q000378:metabolism*
chemical_list: D001426:Bacterial Proteins; D029968:Escherichia coli Proteins; D006586:Hexanes; D007783:Lactones; C504601:LsrR protein, E coli; C090749:LuxP protein, Vibrio; C091088:N-octanoylhomoserine lactone; D010420:Pentanes; D012097:Repressor Proteins; D006714:Homoserine