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  • Review Article
  • Published:

Revisiting the host as a growth medium

Nature Reviews Microbiology volume 6, pages 657–666 (2008)Cite this article

Key Points

  • The ability of a pathogen to cause disease relies on its ability to acquire nutrients in vivo. This Review revisits the concept of the host as a growth medium during infection and outlines the potential of this experimental approach for development of new therapeutics.

  • The carbon source can influence the ability of a pathogen to evade the immune system. Neisseria meningitidis preferentially uses a carbon source which has degradation products that feed directly into the biosynthesis of compounds important for immune evasion.

  • The available carbon source affects site-specific colonization, or tissue tropism, by certain pathogens. Unlike enterohaemorrhagic Escherichia coli (EHEC) strains, uropathogenic E. coli (UPEC) strains can colonize the urinary tract. The ability of UPEC to catabolize D-serine, excreted as a urinary waste product, might help to define this tropism.

  • Carbon resource partitioning is a method used to avoid competition with other organisms. Aggregatibacter actinomycetemcomitans, a slow-growing opportunistic pathogen that is found in the human mouth, uses a non-optimal carbon source that is produced as a waste product by prevalent and fast-growing oral streptococci.

  • Bacteria communicate using diverse chemical signals, and carbon source metabolism can influence production and dissemination of these signals. Pseudomonas aeruginosa responds to aromatic amino acids in cystic fibrosis sputum and increases production of a cell–cell communication signal that is important for interspecies competition and virulence.

  • Many infection sites, as bacterial growth media, remain undefined, and for many pathogens the in vivo carbon source is not known. Much work remains to be done to elucidate bacterial carbon metabolism during infection.

Abstract

The ability of the human body to play host to bacterial pathogens has been studied for more than 200 years. Successful pathogenesis relies on the ability to acquire the nutrients that are necessary for growth and survival, yet relatively little is understood about the in vivo physiology and metabolism of most human pathogens. This Review discusses how in vivo carbon sources can affect disease and highlights the concept that carbon metabolic pathways provide viable targets for antibiotic development.

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Figure 1: Molecular mimicry by Neisseria meningitidis.
Figure 2: Mycobacterium tuberculosis cholesterol catabolism and virulence factor production.
Figure 3: Resource partitioning by oral bacteria.
Figure 4: Cell–cell communication, carbon metabolism and pathogenesis in Pseudomonas aeruginosa.

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Acknowledgements

We would like to acknowledge members of the Whiteley laboratory for critical discussion and review of this manuscript.

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Author notes

  1. Stacie A. Brown and Kelli L. Palmer: These authors contributed equally to this work.

Authors and Affiliations

  1. Section of Molecular Genetics and Microbiology, The University of Texas at Austin, Austin, 78712, Texas, USA

    Stacie A. Brown, Kelli L. Palmer & Marvin Whiteley

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  1. Stacie A. Brown
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  2. Kelli L. Palmer
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Correspondence to Marvin Whiteley.

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DATABASES

Entrez Genome Project

Aggregatibacter actinomycetemcomitans

Agrobacterium tumefaciens

Brucella abortus

Brucella suis

Escherichia coli

Legionella pneumophila

Listeria monocytogenes

Mycobacterium tuberculosis

Neisseria meningitidis

Pseudomonas aeruginosa

Rickettsia conorii

Streptococcus mutans

Toxoplasma gondii

FURTHER INFORMATION

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Glossary

Molecular mimicry

Chemical imitation of a host structural component by a foreign body.

Granuloma

A tissue lesion that occurs when macrophages are unable to clear foreign substances from the body. The centre of a granuloma contains a high density of macrophages (sometimes necrotic), which are surrounded by multiple immune cell types, including polymorphonuclear leukocytes and fibroblasts.

Glyoxylate shunt

An anaplerotic pathway used to bypass CO2-generating reactions of the tricarboxylic acid cycle to conserve carbon for intermediate biosynthesis; required for growth on fatty acids or acetate.

Polyketide

A member of a diverse class of secondary metabolites formed by condensation of small fatty acid groups. Polyketides are produced by bacteria, archaea and eukaryotes and can function as natural antimicrobials.

Phagosome

An intracellular vacuole that is formed by phagocytosis of extracellular components. Phagocytic cells, such as macrophages, are involved in bacterial clearance during infection. Properly trafficked phagosomes fuse with lysosomes — compartments that are filled with degradative enzymes.

Cofactor

A non-proteinaceous chemical compound that is required for enzyme catalysis.

Illegitimate recombination

A type of genetic recombination that occurs in spite of little homology between nucleotide sequences.

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Brown, S., Palmer, K. & Whiteley, M. Revisiting the host as a growth medium. Nat Rev Microbiol 6, 657–666 (2008). https://doi.org/10.1038/nrmicro1955

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