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  • Review Article
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Quorum sensing signal–response systems in Gram-negative bacteria

Nature Reviews Microbiology volume 14, pages 576–588 (2016)Cite this article

Subjects

Key Points

  • Quorum sensing is a cell–cell communication process that enables bacteria to obtain information about cell density and species composition of the vicinal community and adjust their gene expression profiles accordingly. Quorum sensing involves the production, release and detection of extracellular signalling molecules known as autoinducers. Group-wide detection of autoinducers enables bacteria to collectively execute behaviours.

  • Autoinducers are small molecules that control quorum sensing. In Gram-negative bacteria, autoinducers are often produced from S-adenosylmethionine (SAM). Autoinducers interact with specific receptors to elicit behaviours that are controlled by quorum sensing.

  • Quorum sensing receptors are either membrane-bound histidine sensor kinases or cytoplasmic transcription factors.

  • Autoinduction occurs when the detection of autoinducers induces the increased production of the same autoinducer molecule, forming a feed-forward regulatory loop. Other features, such as positive and negative feedback loops and small regulatory RNAs, optimize the integration of the autoinducer-encoded information and provide ideal quorum sensing dynamics.

  • Signal integration is a process that takes place in most Gram-negative bacteria when several autoinducers and receptors work in parallel, or in series, to synchronize functions that are controlled by quorum sensing. Processes such as bioluminescence, the production of virulence factors and the formation of biofilms are controlled by quorum sensing.

  • Quorum sensing shapes the composition of microbial communities. For example, bacterial species in the human gut microbiota produce and respond to autoinducers. There is increasing evidence that quorum sensing controls key physiological processes in the gut and may affect the virulence programmes of invading pathogens. Host cells are also known to produce autoinducer mimics.

  • Synthetic quorum sensing modulators are molecules that agonize or antagonize quorum sensing and they are being developed as anti-virulence medicines. Distinct from traditional antibiotics, quorum sensing modulators do not affect the growth of pathogenic bacteria, but rather, disrupt their virulence programmes.

Abstract

Bacteria use quorum sensing to orchestrate gene expression programmes that underlie collective behaviours. Quorum sensing relies on the production, release, detection and group-level response to extracellular signalling molecules, which are called autoinducers. Recent work has discovered new autoinducers in Gram-negative bacteria, shown how these molecules are recognized by cognate receptors, revealed new regulatory components that are embedded in canonical signalling circuits and identified novel regulatory network designs. In this Review we examine how, together, these features of quorum sensing signal–response systems combine to control collective behaviours in Gram-negative bacteria and we discuss the implications for host–microbial associations and antibacterial therapy.

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Figure 1: Quorum sensing synthases, autoinducers and receptors.
Figure 2: Structures of LuxR-type quorum sensing receptors.
Figure 3: Quorum sensing circuits in Pseudomonas aeruginosa.
Figure 4: Quorum sensing circuits in Vibrio harveyi.
Figure 5: Feedback loops control Vibrio harveyi quorum sensing dynamics.
Figure 6: AI-2-mediated quorum sensing in the mammalian gut.

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Acknowledgements

This work was supported by the Howard Hughes Medical Institute, the US National Institutes of Health (NIH; grant 5R01GM065859) and the US National Science Foundation (grant MCB-0948112 to B.L.B.). K.P. was supported by the Deutsche Forschungsgemeinschaft (DFG; grant PA2820/1).

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Authors and Affiliations

  1. Department of Biology, Ludwig-Maximilians-University Munich, Biocenter, Martinsried, 82152, Germany

    Kai Papenfort

  2. Howard Hughes Medical Institute; Department of Molecular Biology, 329 Lewis Thomas Laboratories, Washington Road, Princeton University,

    Bonnie L. Bassler

  3. Department of Molecular Biology, 329 Lewis Thomas Laboratories, Washington Road, Princeton University, Princeton, 08544, New Jersey, USA

    Bonnie L. Bassler

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  1. Kai Papenfort
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Correspondence to Kai Papenfort or Bonnie L. Bassler.

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Glossary

Public goods

Common-pool resources that are frequently present in biological and social systems. Public goods are available to all members of the community, irrespective of whether a member contributed to their production. Therefore, public goods are prone to exploitation by non-producers.

Two-component systems

A large group of signal-transduction circuits that typically consist of a membrane-bound histidine sensor kinase that detects a specific environmental stimulus and a cognate response regulator that mediates the cellular response, primarily through transcriptional regulation of target genes.

Feed-forward loop

A common regulatory network motif in biological pathways. The feed-forward loop is composed of two input factors (usually transcriptional regulators), one of which regulates the other, such that both factors jointly regulate downstream target genes.

Small RNAs

(sRNAs). Bacterial sRNAs are a heterogeneous group of post-transcriptional regulators that often act in conjunction with the chaperone Hfq.

Bet-hedging

A survival strategy that reduces the temporal variance in fitness at the expense of reduced arithmetic mean fitness.

GAF and PAS domains

Domains that are often conserved in signalling proteins in which they function as ligand-binding domains.

van der Waals interactions

Weak attractive or repulsive forces between molecules or atomic groups that do not result from covalent bonds or electrostatic interactions between ions or ionic groups.

ATP-binding cassette transporter

(ABC transporter). A member of a large superfamily of small molecule transport systems that are present in all phyla.

σ54

An alternative sigma factor in bacteria that is encoded by the rpoN gene, which was originally identified as a regulator of genes that are involved in nitrogen metabolism.

Hfq

A globally acting RNA-binding protein that facilitates the base pairing of bacterial small RNAs with their target mRNAs.

Cyclic dimeric guanosine monophosphate

(c-di-GMP). A second-messenger molecule that is used in signal transduction in various bacteria.

Cyclic adenosine monophosphate

(cAMP). A second-messenger molecule that is important in many biological processes in organisms, ranging from bacteria to humans.

GGDEF and EAL domains

Protein domains that are ubiquitous in bacteria and function to synthesize and degrade the intracellular signalling molecule cyclic dimeric guanosine monophosphate (c-di-GMP), respectively.

Type VI secretion

Systems that are used by Gram-negative bacteria to inject effector proteins and virulence factors from across the interior of one bacterial cell into another cell called the prey.

Horizontal gene transfer

The exchange of genetic information between organisms in a manner other than by traditional reproduction. Horizontal gene transfer is key for the acquisition of antibiotic resistance in bacteria and also has an important role in evolution and the generation of diversity.

Persister cells

Isogenic members of a bacterial population that have entered a non-growing or extremely slow-growing physiological state, which makes them tolerant to a wide range of antimicrobials.

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Papenfort, K., Bassler, B. Quorum sensing signal–response systems in Gram-negative bacteria. Nat Rev Microbiol 14, 576–588 (2016). https://doi.org/10.1038/nrmicro.2016.89

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