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Inter-kingdom signalling: communication between bacteria and their hosts

Key Points

  • This Review discusses inter-kingdom hormonal signalling between bacteria and mammals, and between bacteria and plants. Several bacterial signalling compounds alter mammalian and plant gene expression, and signalling transduction mechanisms. Here, the authors show how mammalian hormones serve as signalling molecules that alter bacterial gene expression.

  • The parallels between signalling through receptor kinases in mammals and prokaryotes are also discussed, as well as the role of hormone receptor functional analogues in eukaryotes and bacteria.

  • Bacteria use adrenaline and noradrenaline to regulate several processes, including virulence, and recent discoveries of bacterial functional analogues of adrenergic receptors have shed light on the adrenergic cross-signalling that occurs between microorganisms and their hosts.

  • Host stress signals are used as signalling molecules by microorganisms. In addition to adrenergic signalling, the authors also discuss recent data that show how other mammalian stress signals, such as dynorphin, are used as signalling molecules by bacterial cells to control virulence-gene expression.

  • Inter-kingdom signalling occurs through lipidic compounds that use intracellular mammalian and bacterial receptors. This Review also addresses how bacterial lipidic signalling molecules, such as acyl homoserine lactones, modulate mammalian cell signalling and the immune system.

  • Finally, the authors discuss evolutionary evidence that some metabolism pathways in eukaryotic cells have evolved through horizontal transfer from bacterial genes.


Microorganisms and their hosts communicate with each other through an array of hormonal signals. This cross-kingdom cell-to-cell signalling involves small molecules, such as hormones that are produced by eukaryotes and hormone-like chemicals that are produced by bacteria. Cell-to-cell signalling between bacteria, usually referred to as quorum sensing, was initially described as a means by which bacteria achieve signalling in microbial communities to coordinate gene expression within a population. Recent evidence shows, however, that quorum-sensing signalling is not restricted to bacterial cell-to-cell communication, but also allows communication between microorganisms and their hosts.

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Figure 1: Chemical structures of bacterial and host signals.
Figure 2: Mammalian signalling through membrane receptors.
Figure 3: Adrenergic sensing in enterohaemorrhagic Escherichia coli.
Figure 4: AHL inter-kingdom signalling.


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Work in the laboratory of V.S. is supported by the National Institutes of Health, The Ellison Medical Foundation and Burroughs Wellcome Fund. The authors thank M. Lyte for comments on this manuscript. They also apologize to the numerous investigators whose manuscripts could not be cited owing to space constraints.

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Correspondence to Vanessa Sperandio.

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Agrobacterium tumefaciens

Borrelia burgdorferi

Escherichia coli

Francisella tularensis

Medicago truncatula

Providencia stuartii

Pseudomonas aeruginosa

Salmonella typhi

Salmonella typhimurium

Sinorhizobium meliloti

Vibrio fischeri

Vibrio parahaemolyticus


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A bacterial hormone-like signalling molecule.

Enteric nervous system

A nervous system that innervates the gastrointestinal tract.


A small organic molecule that is produced by bacteria to sequester iron.

Type III secretion system

A specialized syringe-like secretion system that is used to inject bacterial effectors into host cells.

Haemolytic uraemic syndrome

A complication, caused mostly by Shiga toxin, that can cause the kidneys to shut down and results in high morbidity and mortality.


An epithelial cell in the intestine.

Eicosanoid family

A lipid-based signalling molecule that is best known for its control of the immune response. Prostaglandins are part of the eicosanoid family.

T helper 1 (TH1) response

The actions of CD4 helper T lymphocytes can be summarized by two pathways, TH1 and TH2, on the basis of the cytokines that they produce and their effector functions. During the TH1 response, T helper lymphocytes principally secrete interferon-γ to activate phagocyte-mediated defence, which typically involves intracellular microorganisms.

Paraoxonase family

A three-member gene family that consists of PON1, PON2 and PON3. Mammalian biological functions of paraoxonases remain elusive. However, possible functions include: protection from organophosphate poisoning; a protective role in vascular disease through lipoprotein lipid oxidation; and the limitation of bacterial infection through potential lactonase activity.

PAS and GAF domain

A ubiquitous protein motif that is conserved in prokaryotes and eukaryotes.

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Hughes, D., Sperandio, V. Inter-kingdom signalling: communication between bacteria and their hosts. Nat Rev Microbiol 6, 111–120 (2008).

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