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

Department of Molecular Biology, Howard Hughes Medical Institute, Princeton University, Princeton, New Jersey 08544-1014, USA.
Nature (Impact Factor: 42.35). 10/2005; 437(7059):750-3. DOI: 10.1038/nature03960
Source: PubMed

ABSTRACT Bacteria communicate by means of chemical signal molecules called autoinducers. This process, called quorum sensing, allows bacteria to count the members in the community and to alter gene expression synchronously across the population. Quorum-sensing-controlled processes are often crucial for successful bacterial--host relationships--both symbiotic and pathogenic. Most quorum-sensing autoinducers promote intraspecies communication, but one autoinducer, called AI-2, is produced and detected by a wide variety of bacteria and is proposed to allow interspecies communication. Here we show that some species of bacteria can manipulate AI-2 signalling and interfere with other species' ability to assess and respond correctly to changes in cell population density. AI-2 signalling, and the interference with it, could have important ramifications for eukaryotes in the maintenance of normal microflora and in protection from pathogenic bacteria.

  • Source
    • "However, it has been shown that bacteria possess not only an intra-species but also an inter-species signalling system (Bassler & Losick, 2006; Hughes & Sperandio, 2008). One of the primary bacterial inter-species communication mechanisms is by the luxS-mediated universal signalling system using autoinducer-2 (AI-2) as signalling molecule (Xavier & Bassler, 2005b), with a luxS homologue typical of multiple bacterial species (Pereira, Thompson, & Xavier, 2012). For example, Escherichia coli, Staphylococcus aureus and Listeria monocytogenes use the LuxS/AI-2 signal for regulation of biofilm formation (Miller & Basler, 2001; Pereira et al., 2012; Xavier & Bassler, 2005a). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Bacteria use quorum sensing (QS) to regulate the expression of certain target genes for social behaviour. A LuxS/AI-2 signalling system serves to control the virulence of some pathogenic bacteria by mechanisms such as motility, biofilm formation and attachment, and is typical of the enterohaemorrhagic Escherichia coli O157:H7 (EHEC) associated with infections of the human intestine. The LuxS/AI-2 signalling system presents an interesting potential as antimicrobial target for appropriate AI-2 inhibitors, and thus widens the scope for treatment or prevention of infections by pathogens such as EHEC. Probiotic lactic acid bacteria (LAB) are primary candidates for this approach because of their general acceptability, safety and adaptation to the intestinal and/or food ecosystem. In this paper, we report on Lactobacillus sakei NR28 as a new candidate strain for AI-2 related quorum quenching. It is considered to be a putative probiotic strain and was originally isolated from kimchi, a traditional Korean fermented food known for its special health features. This study has shown that AI-2 activity and the associated virulence factors of the EHEC ‘wild-type’ strain E. coli ATCC 43894, were significantly reduced by L. sakei NR28, while, at the same time, the cell viability of the EHEC strain was not affected. In addition, the purified AI-2 molecule, a luxS-deficient mutant of EHEC strain ATCC 43894, and an AI-2 independent EHEC mimicking strain of Citrobacter rodentium were used to determine the relationship between the virulence reducing effect of L. sakei NR28 and its AI-2 inhibiting ability. Our results showed that L. sakei NR28 has a reducing effect on the pathogenicity of the ‘wild-type’ EHEC strain ATCC 43894 by AI-2 signalling inhibition.
    Food Control 12/2014; 45:62–69. DOI:10.1016/j.foodcont.2014.04.024 · 2.82 Impact Factor
  • Source
    • "The lsrG mutant, which is less efficient in degrading the inducer of the system (AI-2-P), and the repressor mutant (lsrR) are the only mutants that ensue a premature AI-2 internalization. These results are consistent with the previous studies on the characterization of the lsr operon and its regulation (Ren et al. 2004; Xavier and Bassler 2005a, 2005b; Li et al. 2007; Pereira et al. 2009), but here we show the phenotype of extracellular AI-2 accumulation for all the lsr single mutants. Our results show that extracellular AI-2 concentration is affected by every singlegene deletion. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Quorum sensing (QS) regulates the onset of bacterial social responses in function to cell density having an important impact in virulence. AI-2 (autoinducer 2) is a signal that has the peculiarity of mediating both intra-and interspecies bacterial QS. We analyzed the diversity of all components of AI-2 quorum sensing across 44 complete genomes of E. coli and Shigella strains. We used phylogenetic tools to study its evolution and determined the phenotypes of single deletion mutants to predict phenotypes of natural strains. Our analysis revealed many likely adaptive polymorphisms both in gene content and nucleotide sequence. We show that all natural strains possess the signal emitter (the luxS gene) but many lack a functional signal receptor (complete lsr operon) and the ability to regulate extracellular signal concentrations. This result is in striking contrast with the canonical species-specific QS systems where one often finds orphan receptors, without a cognate synthase, but not orphan emitters. Our analysis indicates that selection actively maintains a balanced polymorphism for the presence/absence of a functional lsr operon suggesting diversifying selection on the regulation of signal accumulation and recognition. These results can be explained either by niche specific adaptation, or by selection for a coercive behavior where signal-blind emitters benefit from forcing other individuals in the population to haste in cooperative behaviors.
    Genome Biology and Evolution 12/2012; 5(1). DOI:10.1093/gbe/evs122 · 4.53 Impact Factor
  • Source
    • "Recent work even suggests that these molecules are able to interconvert allowing for the inclusion of mixed bacterial populations in the quorum recognized by a single species (Xavier and Bassler, 2005a). The molecular form of AI-2 produced by C. jejuni is unknown at this time, however, work by our group and others groups has demonstrated that it is active as a luxP ligand during in vitro bioluminescence assays with a Vibrio harveyi reporter strain (Elvers and Park, 2002; Jeon et al., 2003; Quinones et al., 2009; Plummer et al., 2011b). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Several intercellular bacterial communication mechanisms have been identified in a broad range of bacterial species. These systems, collectively termed quorum-sensing systems, have been demonstrated to play significant roles in a variety of bacterial processes including motility, biofilm formation, expression of virulence genes, and animal colonization. Campylobacter jejuni is known to possess a LuxS/ autoinducer-2 (AI-2) mediated system that have been partially characterized over the last decade. AI-2 is formed as a byproduct of the activated methyl recycling pathway, specifically by the LuxS enzyme. Previous work in our laboratory and that of others has demonstrated that this gene is involved in a variety of physiologic pathways of C. jejuni including motility, autoagglutination, cytolethal distending toxin (CDT) expression, flagellar expression, oxidative stress, and animal colonization. This review article will summarize the current research associated with LuxS in C. jejuni and will provide insights into the role of this system in the metabolism and intercellular communication of this organism. Additionally, the evidence for other quorum-sensing pathways in Campylobacter will be discussed.
    Frontiers in Cellular and Infection Microbiology 03/2012; 2:22. DOI:10.3389/fcimb.2012.00022 · 2.62 Impact Factor
Show more


Available from