LsrF, a coenzyme A-dependent thiolase, catalyzes the terminal step in processing the quorum sensing signal autoinducer-2

The quorum sensing signal autoinducer-2 (AI-2) regulates important bacterial behaviors, including biofilm formation and the production of virulence factors. Some bacteria, such as Escherichia coli , can quench the AI-2 signal produced by a variety of species present in the environment, and thus can...

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Veröffentlicht in:Proceedings of the National Academy of Sciences - PNAS 2014-09, Vol.111 (39), p.14235-14240
Hauptverfasser: Marques, João C., Oh, Il Kyu, Ly, Daniel C., Lamosa, Pedro, Ventura, M. Rita, Miller, Stephen T., Xavier, Karina B.
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Sprache:eng
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Zusammenfassung:The quorum sensing signal autoinducer-2 (AI-2) regulates important bacterial behaviors, including biofilm formation and the production of virulence factors. Some bacteria, such as Escherichia coli , can quench the AI-2 signal produced by a variety of species present in the environment, and thus can influence AI-2–dependent bacterial behaviors. This process involves uptake of AI-2 via the Lsr transporter, followed by phosphorylation and consequent intracellular sequestration. Here we determine the metabolic fate of intracellular AI-2 by characterizing LsrF, the terminal protein in the Lsr AI-2 processing pathway. We identify the substrates of LsrF as 3-hydroxy-2,4-pentadione-5-phosphate (P-HPD, an isomer of AI-2-phosphate) and coenzyme A, determine the crystal structure of an LsrF catalytic mutant bound to P-HPD, and identify the reaction products. We show that LsrF catalyzes the transfer of an acetyl group from P-HPD to coenzyme A yielding dihydroxyacetone phosphate and acetyl-CoA, two key central metabolites. We further propose that LsrF, despite strong structural homology to aldolases, acts as a thiolase, an activity previously undescribed for this family of enzymes. With this work, we have fully characterized the biological pathway for AI-2 processing in E. coli , a pathway that can be used to quench AI-2 and control quorum-sensing–regulated bacterial behaviors. Significance Bacteria coordinate behavior through production, release, and detection of chemical signals called autoinducers. While most are species-specific, autoinducer-2 is used by many species and facilitates interspecies communication. Because many important behaviors, including virulence and biofilm formation, are thus regulated, methods for interfering with this communication are regarded as promising alternatives to antibiotics. Some bacteria can manipulate levels of autoinducer-2 in the environment, interfering with the communication of other species. Here we characterize the terminal step in the pathway that Escherichia coli uses to destroy this signal via a novel catalytic mechanism, and identify products that link quorum sensing and primary cell metabolism.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.1408691111