Phosphorylation and processing of the quorum-sensing molecule autoinducer-2 in enteric bacteria

ACS Chem Biol. 2007 Feb 20;2(2):128-36. doi: 10.1021/cb600444h. Epub 2007 Mar 2.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adenosine Triphosphate / metabolism
  • Enterobacteriaceae / metabolism*
  • Escherichia coli Proteins / physiology
  • Homoserine / analogs & derivatives*
  • Homoserine / metabolism
  • Lactones / metabolism*
  • Magnetic Resonance Spectroscopy
  • Mass Spectrometry
  • Pentanes / metabolism
  • Phosphorylation
  • Quorum Sensing*
  • Receptors, Cell Surface / physiology
  • Repressor Proteins / physiology


  • 4,5-dihydroxy-2,3-pentanedione
  • Escherichia coli Proteins
  • Lactones
  • LsrB protein, Salmonella typhimurium
  • LsrR protein, E coli
  • N-octanoylhomoserine lactone
  • Pentanes
  • Receptors, Cell Surface
  • Repressor Proteins
  • Homoserine
  • Adenosine Triphosphate