Helicobacter pylori perceives the quorum-sensing molecule AI-2 as a chemorepellent via the chemoreceptor TlpB

Institute of Molecular Biology, University of Oregon, Eugene, OR 97403, USA.
Microbiology (Impact Factor: 2.56). 05/2011; 157(Pt 9):2445-55. DOI: 10.1099/mic.0.049353-0
Source: PubMed


Helicobacter pylori moves in response to environmental chemical cues using a chemotaxis two-component signal-transduction system. Autoinducer-2 (AI-2) is a quorum-sensing signal produced by the LuxS protein that accumulates in the bacterial environment in a density-dependent manner. We showed previously that a H. pylori luxS mutant was defective in motility on soft agar plates. Here we report that deletion of the luxS gene resulted in swimming behaviour with a reduced frequency of stops as compared to the wild-type strain. Stopping frequency was restored to wild-type levels by genetic complementation of the luxS mutation or by addition of synthetic 4,5-dihydroxy-2,3-pentanedione (DPD), which cyclizes to form AI-2. Synthetic DPD also increased the frequency of stops in wild-type H. pylori, similar to the behaviour induced by the known chemorepellent HCl. We found that whereas mutants lacking the chemoreceptor genes tlpA, tlpC or tlpD responded to an exogenous source of synthetic DPD, the chemoreceptor mutant tlpB was non-responsive to a gradient or uniform distribution of the chemical. Furthermore, a double mutant lacking both tlpB and luxS exhibited chemotactic behaviour similar to the tlpB single mutant, whereas a double mutant lacking both tlpB and the chemotransduction gene cheA behaved like a nonchemotactic cheA single mutant, supporting the model that tlpB functions in a signalling pathway downstream of luxS and upstream of cheA. We conclude that H. pylori perceives LuxS-produced AI-2 as a chemorepellent via the chemoreceptor TlpB.

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Available from: Karen Ottemann, Jul 21, 2014
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    • "Taxis has been observed towards compounds that serve as carbon or energy sources like sugars, amino acids or organic acids (Mesibov and Adler, 1972; Adler et al., 1973; Seymour and Doetsch, 1973; Moulton and Montie, 1979). In addition, chemotaxis has been reported for other classes of compounds like neurotransmitters, plant hormones or quorum sensing signals (Bansal et al., 2007; Antunez-Lamas et al., 2009; Hegde et al., 2011; Rader et al., 2011). Typically, the specificity of a chemotactic response is determined by the chemoreceptor that is at the beginning of the chemosensory signaling cascade. "
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    ABSTRACT: Chemoreceptors are at the beginning of chemosensory pathways that mediate chemotaxis. Pseudomonas putida KT2440 is predicted to have 27 chemoreceptors, most of which uncharacterised. We have previously identified McpS as chemoreceptor for Krebs cycle intermediates. Citrate is primarily present in the environment as metal-complex, which, however, is not recognized by McpS. We show here that the McpS paralogue McpQ recognizes specifically citrate and citrate/metal2+ complexes. The McpQ ligand binding domain (McpQ-LBD) binds citrate/metal2+ complexes with higher affinity than citrate. McpQ-LBD is present in a monomer-dimer equilibrium and citrate and particularly citrate/Mg2+ binding stabilize the dimer. The bacterium showed much stronger responses to citrate/Mg2+ than to citrate and mcpQ inactivation caused a dramatic reduction in chemotaxis. Responses to Krebs cycle intermediates are thus mediated by the broad range McpS and McpQ that responds specifically to an intermediate not recognized by McpS. Interesting parallels exist to the paralogous amino acid chemoreceptors of P. aeruginosa and Bacillus subtilis. Whereas one paralogue recognizes most amino acids, the remaining paralogue binds specifically one of the few acids not recognized by the broad range receptors. Therefore, chemotaxis to compound families by the concerted action of broad and narrow range receptors may represent a general mechanism.
    Environmental Microbiology 08/2015; DOI:10.1111/1462-2920.13030 · 6.20 Impact Factor
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    • "Recently, Rader et al. [12] described that the chemoreceptor TlpB functiones as AI-2 receptor in Helicobacter pylori. Despite of the existence of chemoreceptors in C. jejuni, which would suggest the existence of a corresponding receptor, no TlpB receptor homolog has been found yet. "
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    ABSTRACT: Since the discovery that Campylobacter (C.) jejuni produces Autoinducer 2 (AI-2), various studies have been conducted to explore the function and role of AI-2 in C. jejuni. However, the interpretation of these analyses has been complicated by differences in strain backgrounds, kind of mutation and culture conditions used. Furthermore, all research on AI-2 dependent phenotypes has been conducted with AI-2 synthase (luxS) mutants. This mutation also leads to a disruption of the activated-methyl-cycle. Most studies lack sufficient complementation resulting in not knowing whether phenotypes of luxS mutants depend on disrupted metabolism or lack of AI-2. Additionally, no AI-2 receptor has been found yet. All this contributes to an intensive discussion about the exact role of AI-2 in C. jejuni. Therefore, we examined the impact of different experiment settings on three different C. jejuni luxS mutants on growth and motility (37°C and 42°C). Our study showed that differing phenotypes of C. jejuni luxS mutants depend on strain background, mutation strategy and culture conditions. Furthermore, we complemented experiments with synthetic AI-2 or homocysteine as well as the combination of both. Complementation with AI-2 and AI-2+homocysteine significantly increased the cell number of C. jejuni NCTC 11168ΔluxS in stationary phase compared to the non-complemented C. jejuni NCTC 11168ΔluxS mutant. Genetic complementation of both C. jejuni 81-176 luxS mutants resulted in wild type comparable growth curves. Also swarming ability could be partially complemented. While genetic complementation restored swarming abilities of C. jejuni 81-176ΔluxS, it did not fully restore the phenotype of C. jejuni 81-176::luxS, which indicates that compensatory mutations in other parts of the chromosome and/or potential polar effects may appear in this mutant strain. Also with neither synthetic complementation, the phenotype of the wild type-strains was achieved, suggesting yet another reason for differing phenotypes other than communication and methionine metabolism for C. jejuni luxS mutants.
    PLoS ONE 08/2014; 9(8):e104399. DOI:10.1371/journal.pone.0104399 · 3.23 Impact Factor
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    • "Comparison of tlpB expression in the wild-type and a HPnc5490 deletion strain confirmed down-regulation of the tlpB mRNA as well as TlpB protein levels by HPnc5490. It has been suggested that TlpB senses protons and diverse studies have demonstrated its potential role in pHtaxis , quorum sensing as well as colonization, and inflammation of the gastric mucosa (McGee et al., 2005; Croxen et al., 2006; Williams et al., 2007; Rader et al., 2011). Therefore, HPnc5490, and probably additional H. pylori sRNAs, could play important roles during stress responses or infection, as described for other bacterial pathogens (Papenfort and Vogel, 2010). "
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    ABSTRACT: The Gram-negative Epsilonproteobacterium Helicobacter pylori is considered as one of the major human pathogens and many studies have focused on its virulence mechanisms as well as genomic diversity. In contrast, only very little is known about post-transcriptional regulation and small regulatory RNAs (sRNAs) in this spiral-shaped microaerophilic bacterium. Considering the absence of the common RNA chaperone Hfq, which is a key-player in post-transcriptional regulation in enterobacteria, H. pylori was even regarded as an organism without riboregulation. However, analysis of the H. pylori primary transcriptome using RNA-seq revealed a very complex transcriptional output from its small genome. Furthermore, the identification of a wealth of sRNAs as well as massive antisense transcription indicates that H. pylori uses riboregulation for its gene expression control. The ongoing functional characterization of sRNAs along with the identification of associated RNA binding proteins will help to understand their potential roles in Helicobacter virulence and stress response. Moreover, research on riboregulation in H. pylori will provide new insights into its virulence mechanisms and will also help to shed light on post-transcriptional regulation in other Epsilonproteobacteria, including widespread and emerging pathogens such as Campylobacter.
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