The Small RNA Chaperone Hfq and Multiple Small RNAs Control Quorum Sensing in Vibrio harveyi and Vibrio cholerae

Department of Molecular Biology, Princeton University, Princeton, NJ 08544, USA.
Cell (Impact Factor: 32.24). 08/2004; 118(1):69-82. DOI: 10.1016/j.cell.2004.06.009
Source: PubMed

ABSTRACT Quorum-sensing bacteria communicate with extracellular signal molecules called autoinducers. This process allows community-wide synchronization of gene expression. A screen for additional components of the Vibrio harveyi and Vibrio cholerae quorum-sensing circuits revealed the protein Hfq. Hfq mediates interactions between small, regulatory RNAs (sRNAs) and specific messenger RNA (mRNA) targets. These interactions typically alter the stability of the target transcripts. We show that Hfq mediates the destabilization of the mRNA encoding the quorum-sensing master regulators LuxR (V. harveyi) and HapR (V. cholerae), implicating an sRNA in the circuit. Using a bioinformatics approach to identify putative sRNAs, we identified four candidate sRNAs in V. cholerae. The simultaneous deletion of all four sRNAs is required to stabilize hapR mRNA. We propose that Hfq, together with these sRNAs, creates an ultrasensitive regulatory switch that controls the critical transition into the high cell density, quorum-sensing mode.

Download full-text


Available from: Rahul V Kulkarni, Sep 27, 2015
1 Follower
39 Reads
  • Source
    • "At low cell density, the autokinase domains of CqsS and LuxPQ become phosphorylated and phosphorus is transferred to LuxO [7]. Phospho-LuxO acts to destabilize the hapR mRNA encoding the master quorum sensing regulator HapR [11] [12]. When the concentration of autoinducers produced by growing bacteria reaches a threshold, CqsS and LuxPQ switch from kinase to phosphatase and the flow of phosphorus is reversed. "
    [Show abstract] [Hide abstract]
    ABSTRACT: In Vibrio cholerae, the genes required for biofilm development are repressed by quorum sensing at high cell density due to the accumulation in the medium of two signaling molecules, cholera autoinducer 1 (CAI-1) and autoinducer 2 (AI-2). A significant fraction of toxigenic V. cholerae isolates, however, exhibit dysfunctional quorum sensing pathways. It was reported that transition state analogs of the enzyme methylthioadenosine/S-adenosylhomocysteine nucleosidase (MtnN) required to make AI-2 inhibited biofilm formation in the prototype quorum sensing-deficient strain N16961. This finding prompted us to examine the role of both autoinducers and MtnN in biofilm development and virulence gene expression in a quorum sensing-deficient genetic background. Here we show that deletion of mtnN encoding methylthioadenosine/S-adenosylhomocysteine nucleosidase, cqsA (CAI-1), and/or luxS (AI-2) do not prevent biofilm development. However, two independent mtnN mutants exhibited diminished growth rate and motility in swarm agar plates suggesting that, under certain conditions, MtnN could influence biofilm formation indirectly. Nevertheless, MtnN is not required for the development of a mature biofilm. Copyright © 2015. Published by Elsevier Inc.
    Biochemical and Biophysical Research Communications 04/2015; 461(1). DOI:10.1016/j.bbrc.2015.03.170 · 2.30 Impact Factor
  • Source
    • "The sRNA transcriptomes of the enterics Escherichia coli and Salmonella enterica show substantial overlap; however, some of the orthologous IGRs display different patterns of expression and several sRNAs are present in only one of the species (Raghavan et al. 2012). Differences in sRNA gene contents among bacteria can arise from lineage-specific loss or from the emergence of new sRNAs through duplication (Lenz et al. 2004; Wilderman et al. 2004) or horizontal acquisition (Pichon and Felden 2005; Sittka et al. 2008). An examination of the distribution of sRNAs within the E. coli/Shigella complex showed that the variation in the presence of known sRNAs was dominated by gene loss through deletions (Skippington and Ragan 2012). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Small RNAs (sRNAs) are short, transcribed regulatory elements that are typically encoded in the intergenic regions (IGRs) of bacterial genomes. Several sRNAs, first recognized in Escherichia coli, are conserved among enteric bacteria, but because of the regulatory roles of sRNAs, differences in sRNA repertoires might be responsible for features that differentiate closely related species. We scanned the E. coli MG1655 and Salmonella enterica Typhimurium genomes for non-syntenic IGRs as a potential source of uncharacterized, species-specific sRNAs and found that genome rearrangements have reconfigured several IGRs causing the disruption and formation of sRNAs. Within an IGR that is present in E. coli but was disrupted in Salmonella by a translocation event is an sRNA that is associated with the FNR/CRP global regulators and influences E. coli biofilm formation. A Salmonella-specific sRNA evolved de novo via point mutations that generated a σ(70) promoter sequence in an IGR that arose through genome rearrangement events. The differences in the sRNA pools among bacterial species have previously been ascribed to duplication, deletion or horizontal acquisition. Here we show that genomic rearrangements also contribute to this process by either disrupting sRNA-containing IGRs or by creating IGRs in which novel sRNAs may evolve. © The Author(s) 2015. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.
    Genome Biology and Evolution 01/2015; 7(2). DOI:10.1093/gbe/evv009 · 4.23 Impact Factor
  • Source
    • "In theory, activating sRNAs can be degraded, recycled, or sequestered. The quorum regulatory RNAs (Qrr) sRNAs are Hfq-dependent trans-encoded sRNAs that control vibrio quorum sensing (Lenz et al., 2004). Quorum sensing is a cell-cell communication process that bacteria use to monitor changes in cell-population density and control collective behaviors such as biofilm formation and virulence factor production. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Quorum sensing is a cell-cell communication process that bacteria use to transition between individual and social lifestyles. In vibrios, homologous small RNAs called the Qrr sRNAs function at the center of quorum-sensing pathways. The Qrr sRNAs regulate multiple mRNA targets including those encoding the quorum-sensing regulatory components luxR, luxO, luxM, and aphA. We show that a representative Qrr, Qrr3, uses four distinct mechanisms to control its particular targets: the Qrr3 sRNA represses luxR through catalytic degradation, represses luxM through coupled degradation, represses luxO through sequestration, and activates aphA by revealing the ribosome binding site while the sRNA itself is degraded. Qrr3 forms different base-pairing interactions with each mRNA target, and the particular pairing strategy determines which regulatory mechanism occurs. Combined mathematical modeling and experiments show that the specific Qrr regulatory mechanism employed governs the potency, dynamics, and competition of target mRNA regulation, which in turn, defines the overall quorum-sensing response. Copyright © 2015 Elsevier Inc. All rights reserved.
    Cell 01/2015; 160(1-2):228-240. DOI:10.1016/j.cell.2014.11.051 · 32.24 Impact Factor
Show more