Processing the Interspecies Quorum-sensing Signal Autoinducer-2 (AI-2)

Journal Article · Sat Dec 31 04:00:00 EST 2011 · Journal of Biological Chemistry

DOI:https://doi.org/10.1074/jbc.M111.230227· OSTI ID:1041746

Marques, J; Lamosa, P; Russell, C; Ventura, R; Maycock, C; Semmelhack, M; Miller, S; Xavier, K

The molecule (S)-4,5-dihydroxy-2,3-pentanedione (DPD) is produced by many different species of bacteria and is the precursor of the signal molecule autoinducer-2 (AI-2). AI-2 mediates interspecies communication and facilitates regulation of bacterial behaviors such as biofilm formation and virulence. A variety of bacterial species have the ability to sequester and process the AI-2 present in their environment, thereby interfering with the cell-cell communication of other bacteria. This process involves the AI-2-regulated lsr operon, comprised of the Lsr transport system that facilitates uptake of the signal, a kinase that phosphorylates the signal to phospho-DPD (P-DPD), and enzymes (like LsrG) that are responsible for processing the phosphorylated signal. Because P-DPD is the intracellular inducer of the lsr operon, enzymes involved in P-DPD processing impact the levels of Lsr expression. Here we show that LsrG catalyzes isomerization of P-DPD into 3,4,4-trihydroxy-2-pentanone-5-phosphate. We present the crystal structure of LsrG, identify potential catalytic residues, and determine which of these residues affects P-DPD processing in vivo and in vitro. We also show that an lsrG deletion mutant accumulates at least 10 times more P-DPD than wild type cells. Consistent with this result, we find that the lsrG mutant has increased expression of the lsr operon and an altered profile of AI-2 accumulation and removal. Understanding of the biochemical mechanisms employed by bacteria to quench signaling of other species can be of great utility in the development of therapies to control bacterial behavior.

• Research Organization: BROOKHAVEN NATIONAL LABORATORY (BNL)
• Sponsoring Organization: USDOE SC OFFICE OF SCIENCE (SC)
• DOE Contract Number: AC02-98CH10886
• OSTI ID: 1041746
• Report Number(s): BNL--97424-2012-JA
• Journal Information: Journal of Biological Chemistry, Journal Name: Journal of Biological Chemistry Journal Issue: 20 Vol. 286; ISSN 0021-9258; ISSN JBCHA3
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
60 APPLIED LIFE SCIENCES
BACTERIA
BUILDUP
CATALYSIS
CONTROL
CRYSTAL STRUCTURE
ENZYMES
IN VITRO
IN VIVO
ISOMERIZATION
LEVELS
MOLECULES
MUTANTS
PHOSPHOTRANSFERASES
PRECURSOR
PROTEIN STRUCTURE
REMOVAL
RESIDUES
SIGNALS
TRANSPORT
UPTAKE
VIRULENCE