Perspective abstract
Nature Chemical Biology 2, 132 - 138 (2006)
Published online: 14 February 2006 | doi:10.1038/nchembio771
How pathogenic bacteria evade mammalian sabotage in the battle for iron
Michael A Fischbach1, Hening Lin2, David R Liu3 & Christopher T Walsh2
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.
- Michael A. Fischbach is in the Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, 240 Longwood Avenue, Boston, Massachusetts 02115, USA and at the Howard Hughes Medical Institute and the Department of Chemistry and Chemical Biology, Harvard University, 12 Oxford Street, Cambridge, Massachusetts 02138, USA.
- Hening Lin and Christopher T. Walsh are in the Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, 240 Longwood Avenue, Boston, Massachusetts 02115, USA. e-mail: christopher_walsh@hms.harvard.edu
- David R. Liu is at the Howard Hughes Medical Institute and the Department of Chemistry and Chemical Biology, Harvard University, 12 Oxford Street, Cambridge, Massachusetts 02138, USA.
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