Iron Tug of War

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Science  28 Nov 2008:
Vol. 322, Issue 5906, pp. 1304
DOI: 10.1126/science.322.5906.1304a

Iron is an essential component of many enzymes, and microbes synthesize and secrete siderophores—small molecules that bind avidly to free iron in soils and in oceans—for the purpose of sequestering as much of it as they can. Many of these siderophores contain 2,3-dihydroxybenzoic acid (2,3-DHBA) as an ironchelating moiety; not coincidentally, the mammalian innate immunity protein siderocalin defends against pathogens by enveloping 2,3-DHBA siderophores and thus blocking bacterial iron acquisition. The anthrax bacterium makes petrobactin, a siderophore that uses the less common 3,4-DHBA as its iron chelator, which enables it to evade the clutches of siderocalin.

Using biochemical and structural analyses, Pfleger et al. show that the Bacillus anthracis protein AsbF catalyzes the conversion of 3-dehydroshikimate (3-DHS) into 3,4-DHBA via a manganese-dependent formation of an enolate intermediate, followed by elimination of the C5 hydroxyl. Why does this matter? These authors show that deleting asbF from an otherwise deadly strain of B. anthracis abolishes virulence in a mouse model of inhalation anthrax. Petrobactin is produced by other pathogenic Bacillus species, and Fox et al. demonstrate that AsbF from a B. thuringiensis strain also dehydrates 3-DHS. — GJC

Proc. Natl. Acad. Sci. U.S.A. 105, 17133 (2008); Biochemistry 47, 10.1021/bi801876q (2008).

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