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  • Review Article
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Metabolic crosstalk between host and pathogen: sensing, adapting and competing

Key Points

  • During an infection the metabolic networks of the host and the bacterial pathogen become interlinked. These interactions between the host and pathogen metabolism influence both bacterial virulence and host responses, which determine the outcome of infection.

  • Bacterial pathogens use metabolic cues provided by the host microenvironment to evaluate their location and alter their gene expression and metabolic networks. These cues can be induced directly by the invading pathogen or are provided by environment-specific metabolites.

  • The host immune response detects metabolites produced by invading pathogens and expresses effector mechanisms that poison bacteria-specific metabolic pathways. Recently defined 'virulence genes' of pathogens include modified or expanded metabolic networks that evade immune mechanisms.

  • Bacterial pathogens and mammalian cells use similar metabolic pathways that share intermediates. The overlap between these networks is a potential source of competition between the host and pathogen during infection. Amino acids, such as tryptophan, asparagine and arginine, are particularly important nutrients that are central to the host–pathogen interaction.

  • Host metabolic diseases, such as diabetes mellitus, increase the risk of bacterial infections, and the interlinked metabolism between the host and pathogen may act as a target for therapeutic intervention. Therefore, modulating host metabolic pathways is a promising approach to treat infections.

Abstract

Our understanding of bacterial pathogenesis is dominated by the cell biology of the host–pathogen interaction. However, the majority of metabolites that are used in prokaryotic and eukaryotic physiology and signalling are chemically similar or identical. Therefore, the metabolic crosstalk between pathogens and host cells may be as important as the interactions between bacterial effector proteins and their host targets. In this Review we focus on host–pathogen interactions at the metabolic level: chemical signalling events that enable pathogens to sense anatomical location and the local physiology of the host; microbial metabolic pathways that are dedicated to circumvent host immune mechanisms; and a few metabolites as central points of competition between the host and bacterial pathogens.

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Figure 1: Host–pathogen interactions as a metabolic system.
Figure 2: Bacteria alter virulence gene expression and growth in response to host derived cues.
Figure 3: Bacteria alter their metabolic networks to adapt to changing host microenvironments following inflammation and immunity.
Figure 4: Amino acids are central to the host–pathogen metabolic interaction.

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Acknowledgements

This work was supported by the US National Institutes of Health (NIH; grants AI064282, AI095208, AI107774 to C.M.S.). The authors thank colleagues in the Behar, Kornfeld and Sassetti laboratories for thoughtful discussions in relation to this manuscript.

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PowerPoint slides

Glossary

Pathogen-associated molecular patterns

(PAMPs). Conserved microbial structures, such as peptidoglycan fragments, that are detected by the host innate immune system and initiate an immune response.

Two-component system

A simple stimulus–response network in which a sensor kinase is activated by a particular stimulus and subsequently transfers a phosphate moiety to a response regulator, enabling it to alter gene expression.

Type III secretion system

A multiprotein virulence complex that acts to translocate bacterial effectors into the cytosol of the host cell to manipulate cellular functions.

Quorum sensing

A process by which bacterial cell density triggers the activation, or repression, of distinct gene expression networks usually through the secretion and detection of small molecules.

Persistence

The ability of a pathogen to remain viable despite stresses, such as immune insults or antibiotic exposure.

Quiescence

A state of low or absent growth in which a microorganism remains metabolically active. This state should be contrasted with true microbial 'dormancy', in which spore-like cells are metabolically inactive.

Stasis

A period of time when the overall net growth of a bacterial population is zero even though growth and death are occurring simultaneously.

Kynurenines

Metabolic by-products of tryptophan metabolism that directly or indirectly alter inflammation and T cell activation.

Indole

A metabolite in the tryptophan biosynthesis pathway that can be used as a precursor for tryptophan anabolism or is a by-product of tryptophan catabolism.

Saprophytic organisms

Organisms that live on dead or decomposing matter, particularly soil-dwelling environmental bacteria.

Anaplerotic pathway

A biochemical pathway that produces metabolites to replenish the intermediates of a metabolic cycle, such as the TCA cycle.

Necrotic granulomas

A Mycobacterium tuberculosis-associated granuloma structure that surrounds a mass of necrotic material.

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Olive, A., Sassetti, C. Metabolic crosstalk between host and pathogen: sensing, adapting and competing. Nat Rev Microbiol 14, 221–234 (2016). https://doi.org/10.1038/nrmicro.2016.12

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