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

Karina B. Xavier, Stephen T. Miller, Wenyun Lu, Jeong Hwan Kim, Joshua Rabinowitz, István Pelczer, Martin F. Semmelhack, Bonnie L. Bassler

Research output: Contribution to journalArticlepeer-review

140 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)128-136
Number of pages9
JournalACS chemical biology
Volume2
Issue number2
DOIs
StatePublished - Feb 2007

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Medicine

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