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Did you know there’s a war going on in your body, right now? It’s all about getting and hoarding Iron. A Siderophore “iron carrier” Iron(III) Siderophore ready for transport It’s an arms race between the mammalian immune system and bacteria in the search for iron: enterobactin transferrin a) enterobactin removes iron from transferrin b) siderocalin intercepts the ferric complex of enterobactin siderocalin c) bacteria produce alternative siderophores such as salmochelin. salmochelin Anthrax siderophores http://www.berkeley.edu/news/media/releases/2006/11/30_siderophore.shtml “Bacterial-Host Iron Wars” BERKELEY – University of California, Berkeley Bacteria need iron to grow. • In iron-poor microenvironments, biosynthetic genes to make, secrete, and retrieve siderophores • Siderophores scavenge ferric iron from the environment. Mammalian hosts fight back • They sequester iron in serum via serum albumin and siderocalin. • virulent bacteria counterattack by an unusual enzymatic Cglycosylation of the enterobactin scaffold, generating salmochelins (first detected in virulent salmonella) • bulky glucosyl moiety prevents sequestration of this tailored siderophore by siderocalin, allowing retrieval of the iron-loaded form by the bacteria. Anthrax bacteria require two siderophores working by two different mechanisms. • Siderocalin, the human immune protein, binds the anthrax bacillibactin siderophore and effectively sidelines it. • a second "stealth" iron scavenger, petrobactin, to get around the human defense against the first scavenger. Petrobactin is not bound by siderocalin. siderocalin Fe-enterobactin Why do we need all that Fe? Hemes in Hemoglobin and Cytochromes