Let LuxS speak up in AI-2 signaling

doi:10.1016/j.tim.2006.01.003

Trends in Microbiology

Volume 14, Issue 3, March 2006, Pages 114-119

https://doi.org/10.1016/j.tim.2006.01.003 Get rights and content

Quorum sensing is a process of bacterial cell–cell communication that uses small diffusible molecules to coordinate diverse behaviors in response to population density. The only quorum-sensing system shared by Gram-positive and Gram-negative bacteria involves the production of autoinducer-2 (AI-2). The AI-2 synthase LuxS is widely distributed among the Bacteria, which suggests that AI-2 is a language for interspecies communication. However, LuxS is also an integral component of the activated methyl cycle in bacteria. LuxS-based quorum sensing has been intensively studied in the past decade, mostly in relation to the AI-2 molecule and the downstream effects of luxS knockouts; few studies have focused on the gene and protein activity itself. Ongoing attempts to dissect the metabolic and signaling roles of LuxS leave little doubt that unraveling the regulation of luxS expression and cellular LuxS activity is the key to understanding LuxS-based quorum sensing.

Section snippets

The playground of the LuxS enzyme: intriguing yet not delineated

Bacteria regulate gene expression in response to a variety of extracellular signals to enable them to adapt to different environmental conditions. Signals can be generated by the bacteria themselves as a function of their population density and many bacteria use these molecules to communicate and coordinate social activities, a process referred to as quorum sensing [1]. Initially, it was believed that the signaling molecules produced by one species served for private conversations (i.e.

The role of LuxS as AI-2 synthase

AI-2 is produced from S-adenosylmethionine (SAM) in at least three enzymatic steps [12] (Figure 1a). Consumption of SAM as a methyl donor produces S-adenosylhomocysteine (SAH), which is subsequently detoxified by the nucleosidase Pfs to yield adenine and S-ribosylhomocysteine (SRH). SRH is converted to 4,5-dihydroxy-2,3-pentanedione (DPD) and homocysteine. This reaction is catalyzed by LuxS [9]. DPD spontaneously rearranges into AI-2 [12]. It was reported that, in Escherichia coli, LuxS is also

LuxS and recycling of S-adenosylhomocysteine (SAH)

LuxS has an important function in the activated methyl cycle of the cell because it is necessary for recycling of the toxic intermediate SAH [7] (Figure 1). Because of its structural similarity to SAM, SAH is a potent feedback inhibitor of the SAM-dependent methyltransferases [20]. Except for some symbionts and parasites, all organisms have a pathway to recycle SAH, either using a two-step enzymatic conversion by the Pfs and LuxS enzymes to produce adenine, homocysteine and DPD, or a one-step

luxS mutants

The function of AI-2 in different species has been studied by constructing luxS mutants and scoring for phenotypes that could be complemented by adding conditioned medium of the corresponding wild-type strain. However, conditioned media are not the proper AI-2 source for complementation assays. Conditioned media prepared from wild-type and luxS mutant strains are likely to differ not only in AI-2 but also in many other aspects (e.g. because of the disruption of the activated methyl cycle) 7, 21

Motifs in LuxS

LuxS is a small metalloenzyme (±170 amino acids). Sequence alignment (Figure 3) reveals an invariant His-Xaa-Xaa-Glu-His motif, which is often found in Zn²⁺-containing proteins. The crystal structures of LuxS from several bacterial species have been determined to high resolution 9, 33, 34. These studies revealed that LuxS exists as a homodimer and that two identical active sites are formed at the dimer interface by residues from both subunits. Each active site contains a divalent metal ion,

Regulation of luxS expression

Some studies have been published on the regulation of luxS expression in E. coli and S. typhimurium. In E. coli, luxS transcription is induced by acid 41, 42. Moreover, E. coli AI-2 synthesis is subject to catabolite repression through the cAMP–cAMP receptor protein (cAMP–CRP) complex, which indirectly represses luxS expression: the cAMP–CRP complex does not bind to the luxS promoter [23]. The expression of pfs was decreased in the presence of glucose; however, this probably occurs through a

Relationship between LuxS and AI-2 levels

Usually, luxS expression is studied indirectly by determining the extracellular AI-2 levels in different environmental and genetic conditions. However, as mentioned earlier, the transcription profile of luxS during bacterial growth does not coincide with the accumulation profile of AI-2 in the bacterial culture fluid. In most bacteria that were examined, extracellular AI-2 activity peaks in mid-to-late exponential phase and declines precipitously in stationary phase. In S. typhimurium 22, 46

Other players in the LuxS playground

An exciting development in recent years is the discovery that bacteria ‘talk to each other’, thereby mimicking a multicellular organization. The AI-2 signal molecule is a fascinating signal because it is produced and interpreted by a variety of bacteria [4]. Substantial research has already provided insight into the complex AI-2-mediated processes. However, there is an assumption that, if a luxS mutant has a phenotype, then cell–cell signaling must be involved in regulating that phenotype.

Acknowledgements

We apologize to the many researchers studying AI-2 and LuxS whose publications could not be cited owing to space limitations. This work was supported by the IWT-Vlaanderen through research project GBOU-20160.

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Citation Excerpt :
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Trends in Microbiology

Let LuxS speak up in AI-2 signaling

Section snippets

The playground of the LuxS enzyme: intriguing yet not delineated

The role of LuxS as AI-2 synthase

LuxS and recycling of S-adenosylhomocysteine (SAH)

luxS mutants

Motifs in LuxS

Regulation of luxS expression

Relationship between LuxS and AI-2 levels

Other players in the LuxS playground

Acknowledgements

Curr. Opin. Microbiol.

Trends Microbiol.

J. Biol. Chem.

Structure

Adv. Appl. Microbiol.

Mol. Cell

Cell

J. Biol. Chem.

Curr. Opin. Microbiol.

Curr. Biol.

Cell

Cell

Curr. Opin. Microbiol.

Curr. Opin. Chem. Biol.

J. Mol. Biol.

Census and consensus in bacterial ecosystems: the LuxR-LuxI family of quorum-sensing transcriptional regulators

Annu. Rev. Microbiol.

Multiple signaling systems controlling expression of luminescence in Vibrio harveyi: sequence and function of genes encoding a second sensory pathway

Mol. Microbiol.

Quorum sensing in Escherichia coli, Salmonella typhimurium, and Vibrio harveyi: a new family of genes responsible for autoinducer production

Proc. Natl. Acad. Sci. U. S. A.

Making ‘sense’ of metabolism: autoinducer-2, LuxS and pathogenic bacteria

Nat. Rev. Microbiol.

LuxS: its role in central metabolism and the in vitro synthesis of 4-hydroxy-5-methyl-3(2H)-furanone

Microbiology

Is autoinducer-2 a universal signal for interspecies communication: a comparative genomic and phylogenetic analysis of the synthesis and signal transduction pathways

BMC Evol. Biol.

The LuxS family of bacterial autoinducers: biosynthesis of a novel quorum-sensing signal molecule

Mol. Microbiol.

Bacteria–host communication: the language of hormones

Proc. Natl. Acad. Sci. U. S. A.

Structural identification of a bacterial quorum-sensing signal containing boron

Nature

Interference with AI-2-mediated bacterial cell–cell communication

Nature