title: Phosphorylation and processing of the quorum-sensing molecule autoinducer-2 in enteric bacteria.
abstract: Quorum sensing is a process of chemical communication that bacteria use to assess cell population density and synchronize behavior on a community-wide scale. Communication is mediated by signal molecules called autoinducers. The LuxS autoinducer synthase produces 4,5-dihydroxy-2,3-pentanedione (DPD), the precursor to a set of interconverting molecules that are generically called autoinducer-2 (AI-2). In enteric bacteria, AI-2 production induces the assembly of a transport apparatus (called the LuxS regulated (Lsr) transporter) that internalizes endogenously produced AI-2 as well as AI-2 produced by other bacterial species. AI-2 internalization is proposed to be a mechanism enteric bacteria employ to interfere with the signaling capabilities of neighboring species of bacteria. We have previously shown that Salmonella enterica serovar Typhimurium binds a specific cyclic derivative of DPD. Here we show that following internalization, the kinase LsrK phosphorylates carbon-5 of the open form of DPD. Phosphorylated DPD (P-DPD) binds specifically to the repressor of the lsr operon, LsrR, consistent with P-DPD being the inducer of the lsr operon. Subsequently, LsrG catalyzes the cleavage of P-DPD producing 2-phosphoglycolic acid. This series of chemical events is proposed to enable enteric bacteria to respond to the presence of competitor bacteria by sequestering and destroying AI-2, thereby eliminating the competitors' intercellular communication capabilities.
authors.affiliation: Department of Molecular Biology, Princeton University, Princeton, New Jersey 08544-1014, USA.
authors.forename: Karina B
authors.initials: KB
authors.lastname: Xavier
authors.forename: Stephen T
authors.initials: ST
authors.lastname: Miller
authors.forename: Wenyun
authors.initials: W
authors.lastname: Lu
authors.forename: Jeong Hwan
authors.initials: JH
authors.lastname: Kim
authors.forename: Joshua
authors.initials: J
authors.lastname: Rabinowitz
authors.forename: István
authors.initials: I
authors.lastname: Pelczer
authors.forename: Martin F
authors.initials: MF
authors.lastname: Semmelhack
authors.forename: Bonnie L
authors.initials: BL
authors.lastname: Bassler
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D004755:Enterobacteriaceae / Q000378:metabolism*; D029968:Escherichia coli Proteins / Q000502:physiology; D006714:Homoserine / Q000031:analogs & derivatives* / Q000378:metabolism; D007783:Lactones / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D010420:Pentanes / Q000378:metabolism; D010766:Phosphorylation; D053038:Quorum Sensing; D011956:Receptors, Cell Surface / Q000502:physiology; D012097:Repressor Proteins / Q000502:physiology
chemical_list: C493138:4,5-dihydroxy-2,3-pentanedione; D029968:Escherichia coli Proteins; D007783:Lactones; C492714:LsrB protein, Salmonella typhimurium; C504601:LsrR protein, E coli; C091088:N-octanoylhomoserine lactone; D010420:Pentanes; D011956:Receptors, Cell Surface; D012097:Repressor Proteins; D006714:Homoserine; D000255:Adenosine Triphosphate