Mammalian Siderophores, Siderophore-binding Lipocalins, and the Labile Iron Pool

Bacteria use tight-binding, ferric-specific chelators called siderophores to acquire iron from the environment and from the host during infection; animals use proteins such as transferrin and ferritin to transport and store iron. Recently, candidate compounds that could serve endogenously as mammalian siderophore equivalents have been identified and characterized through associations with siderocalin, the only mammalian siderophore-binding protein currently known. Siderocalin, an antibacterial protein, acts by sequestering iron away from infecting bacteria as siderophore complexes. Candidate endogenous siderophores include compounds that only effectively transport iron as ternary complexes with siderocalin, explaining pleiotropic activities in normal cellular processes and specific disease states. Bacteria use tight-binding, ferric-specific chelators called siderophores to acquire iron from the environment and from the host during infection; animals use proteins such as transferrin and ferritin to transport and store iron. Recently, candidate compounds that could serve endogenously as mammalian siderophore equivalents have been identified and characterized through associations with siderocalin, the only mammalian siderophore-binding protein currently known. Siderocalin, an antibacterial protein, acts by sequestering iron away from infecting bacteria as siderophore complexes. Candidate endogenous siderophores include compounds that only effectively transport iron as ternary complexes with siderocalin, explaining pleiotropic activities in normal cellular processes and specific disease states. Iron is required by virtually all living things (1Nadadur S.S. Srirama K. Mudipalli A. Iron transport and homeostasis mechanisms: their role in health and disease.Indian J. Med. 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Bluhm M.E. Raymond K.N. Strong R.K. The neutrophil lipocalin NGAL is a bacteriostatic agent that interferes with siderophore-mediated iron acquisition.Mol. Cell. 2002; 10: 1033-1043Abstract Full Text Full Text PDF PubMed Scopus (1076) Google Scholar, 58Abergel R.J. Moore E.G. Strong R.K. Raymond K.N. Microbial evasion of the immune system: structural modifications of enterobactin impair siderocalin recognition.J. Am. Chem. Soc. 2006; 128: 10998-10999Crossref PubMed Scopus (55) Google Scholar, 59Abergel R.J. Wilson M.K. Arceneaux J.E. Hoette T.M. Strong R.K. Byers B.R. Raymond K.N. Anthrax pathogen evades the mammalian immune system through stealth siderophore production.Proc. Natl. Acad. Sci. U.S.A. 2006; 103: 18499-18503Crossref PubMed Scopus (161) Google Scholar, 62Flo T.H. Smith K.D. Sato S. Rodriguez D.J. Holmes M.A. Strong R.K. Akira S. Aderem A. 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Endogenous iron transport systems alternative to Tf have been hypothesized based on the phenotype of hypotransferrinemic mice and at