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How pathogenic bacteria evade mammalian sabotage in the battle for iron

Nature Chemical Biology volume 2, pages 132–138 (2006)Cite this article

Abstract

Many bacteria, including numerous human pathogens, synthesize small molecules known as siderophores to scavenge iron. Enterobactin, a siderophore produced by enteric bacteria, is surprisingly ineffective as an iron-scavenging agent for bacteria growing in animals because of its hydrophobicity and its sequestration by the mammalian protein siderocalin, a component of the innate immune system. However, pathogenic strains of Escherichia coli and Salmonella use enzymes encoded by the iroA gene cluster to tailor enterobactin by glycosylation and linearization. The resulting modified forms of enterobactin, known as salmochelins, can evade siderocalin and are less hydrophobic than enterobactin, restoring this siderophore's iron-scavenging ability in mammals.

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Figure 1
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Figure 5: Processing of Ent by iroA-encoded enzymes.
Figure 6: Overview of the microcin E492 system.

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Acknowledgements

Research in the authors' laboratories is supported by National Institutes of Health grants AI042738 (to C.T.W.) and GM065400 (to D.R.L.), and by the Howard Hughes Medical Institute (D.R.L.). M.A.F. is supported by a predoctoral fellowship from the Hertz Foundation, and H.L. is supported by a postdoctoral fellowship from the Jane Coffin Childs Memorial Fund. We are grateful to K. Hantke (Universität Tübingen) for helpful discussions.

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  1. Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, 240 Longwood Avenue, Boston, 02115, Massachusetts, USA

    Michael A Fischbach

  2. Howard Hughes Medical Institute and the Department of Chemistry and Chemical Biology, Harvard University, 12 Oxford Street, Cambridge, 02138, Massachusetts, USA

    Michael A Fischbach

  3. the Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, 240 Longwood Avenue, Boston, 02115, Massachusetts, USA

    Hening Lin & Christopher T Walsh

  4. the Howard Hughes Medical Institute and the Department of Chemistry and Chemical Biology, Harvard University, 12 Oxford Street, Cambridge, 02138, Massachusetts, USA

    David R Liu

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Fischbach, M., Lin, H., Liu, D. et al. How pathogenic bacteria evade mammalian sabotage in the battle for iron. Nat Chem Biol 2, 132–138 (2006). https://doi.org/10.1038/nchembio771

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