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Signalling

Listening in on bacteria: acyl-homoserine lactone signalling

Nature Reviews Molecular Cell Biology volume 3, pages 685–695 (2002)Cite this article

Key Points

  • Bacteria can communicate with each other using diffusible chemical signals and can co-ordinate their behaviour to function as a group. Interbacterial signalling that functions to reflect population density is described as quorum sensing.

  • Among Gram-negative bacteria, acylated-homoserine lactones (acyl-HSLs) are common quorum-sensing signals that regulate a diverse range of target functions, which are often involved in host interactions.

  • Under certain circumstances, at least, quorum sensing has a role in the development of sessile microbial populations — called microbial biofilms — for several different bacteria, including the opportunistic human pathogens Pseudomonas aeruginosa and Burkholderia cepacia.

  • Acyl-HSLs are synthesized from common fatty-acid and amino-acid precursors, most commonly through proteins of the LuxI family of acyl-HSL synthases, although alternate biosynthetic routes have been identified in a few cases.

  • Increases in acyl-HSL concentration are generally perceived through the activity of LuxR-type transcription factors that bind the signals and are subsequently modified in their DNA-binding activity. Most LuxR proteins are transcriptional activators, although a few acyl-HSL-responsive repressors have also been identified.

  • The recently obtained three-dimensional structure of a LuxR-type protein reveals potential mechanisms for its interactions with both the relevant acyl-HSL and the DNA sequences upstream of regulated target genes.

  • Acyl-HSL quorum sensing might provide new targets for drug therapies.

  • Other well-studied mechanisms of bacterial quorum-sensing include oligopeptide signal molecules in Gram-positive bacteria and the potential interspecies signal, formerly known as autoinducer-2 (furanosyl boron diester), which is produced by a diverse range of microorganisms.

Abstract

Bacterial cell-to-cell signalling has emerged as a new area in microbiology. Individual bacterial cells communicate with each other and co-ordinate group activities. Although a lot of detail is known about the mechanisms of a few well-characterized bacterial communication systems, other systems have been discovered only recently. Bacterial intercellular communication has become a target for the development of new anti-virulence drugs.

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Figure 1: Vibrio fischeri lux-gene organization and symbiotic bioluminescence.
Figure 2: Model of acyl-homoserine-lactone (acyl-HSL) quorum sensing in a single generalized bacterial cell.
Figure 3: Structure and function of LuxI-type acyl-homoserine-lactone (acyl-HSL) synthases.
Figure 4: Structure and function of LuxR-type transcription factors.

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Acknowledgements

We thank our many colleagues, who make the area of cell-to-cell bacterial communication so exciting. Specifically, we gratefully acknowledge S. von Bodman, M. Churchill, A. Stevens and S. Winans for sharing their unpublished results, and D. Bartels, Aurora Biosciences, for help in drafting the Box 3 figure. C.F. receives support from the National Science Foundation and the United States Department of Agriculture. E.P.G. acknowledges the generous support of the National Institutes of Health, the National Science Foundation, the Cystic Fibrosis Foundation, Procter & Gamble and the W. M. Keck Foundation.

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Authors and Affiliations

  1. Department of Biology, Indiana University, Jordan Hall 142, 1001 East 3rd Street, Bloomington, 47405, Indiana, USA

    Clay Fuqua

  2. Department of Microbiology, University of Iowa, Iowa City, 52242, Iowa, USA

    E. Peter Greenberg

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  1. Clay Fuqua
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  2. E. Peter Greenberg
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Correspondence to E. Peter Greenberg.

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DATABASES

SwissProt

agrA

agrB

AgrC

agrD

ainR

ainS

CarR

EsaI

HdtS

hla

lacZ

LasI

LasR

luxA

luxB

luxC

luxD

luxE

LuxI

LuxR

luxS

RhlI

RhlR

TraR

VanM

Glossary

GENETIC COMPETENCE

The ability to take up naked DNA from the external environment through the process of transformation.

PROTEOBACTERIA

A large, physiologically diverse phylogenetic group of Gram-negative bacteria, also known as the purple bacteria.

TWO-COMPONENT SYSTEMS

A common bacterial signal-transduction system that is composed of at least two components — a sensor kinase (which alters its rate of autophosphorylation in response to specific environmental conditions) and a response regulator (to which the phosphate group is transferred, and which transduces the regulatory signal to cellular processes such as gene expression).

EXOENZYME

An enzyme that is secreted to the external environment across the bacterial envelope.

BIOFILMS

Surface-adherent microbial populations, usually embedded within a self-produced matrix material.

ACYL CARRIER PROTEIN

Conserved protein required for fatty-acid biosynthesis. Fatty-acid intermediates are covalently associated with acyl carrier protein through the phosphopantethiene prosthetic group.

BACTERIAL ENVELOPE

The cell wall and cytoplasmic membrane of a bacterial cell.

−35 REGION

Consensus sequence region of standard prokaryotic promoters ∼35 base pairs upstream of the transcriptional start site.

σ SUBUNIT

Subunit of the prokaryotic RNA polymerase holoenzyme that recognizes and binds to the promoter sequence and dissociates after transcription begins.

−10 REGION

Consensus sequence region of standard prokaryotic promoters ∼10 base pairs upstream of the transcriptional start site.

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Fuqua, C., Greenberg, E. Listening in on bacteria: acyl-homoserine lactone signalling. Nat Rev Mol Cell Biol 3, 685–695 (2002). https://doi.org/10.1038/nrm907

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