Iron Metabolism in Pathogenic Bacteria

Abstract

The ability of pathogens to obtain iron from transferrins, ferritin, hemoglobin, and other iron-containing proteins of their host is central to whether they live or die. To combat invading bacteria, animals go into an iron-withholding mode and also use a protein (Nramp1) to generate reactive oxygen species in an attempt to kill the pathogens. Some invading bacteria respond by producing specific iron chelators-siderophores-that remove the iron from the host sources. Other bacteria rely on direct contact with host iron proteins, either abstracting the iron at their surface or, as with heme, taking it up into the cytoplasm. The expression of a large number of genes (>40 in some cases) is directly controlled by the prevailing intracellular concentration of Fe(II) via its complexing to a regulatory protein (the Fur protein or equivalent). In this way, the biochemistry of the bacterial cell can accommodate the challenges from the host. Agents that interfere with bacterial iron metabolism may prove extremely valuable for chemotherapy of diseases.

Enterobactin Protonation and Iron Release: Structural Characterization of the Salicylate Coordination Shift in Ferric Enterobactin1

“…21,22 Despite thorough literature precedent, [21][22][23][24] confusion about coordination geometry at the metal center has persisted. 25 Previous studies suggested a structural change for the ferric enterobactin complex from a catecholate to salicylate geometry around the metal ion, where protonation occurs at the meta-hydroxyl oxygen of the catechol, and coordination of Fe(III) shifts from the two catecholate oxygens to the ortho-hydroxyl oxygen and the amide oxygen ( Figure 1). 23,24 The work presented here confirms the solution and solid state structural alteration of ferric enterobactin upon protonation.…”

Stress and microbial endocrinology: prospects for ruminant nutrition

“…Research from our laboratories and those of others have shown that NA, adrenaline and dopamine and certain of their metabolites (such as dihydroxymandelic acid and dihydroxyphenylglycol; Freestone et al, 2002 and all share the ability to stimulate growth in serum or blood growth by enabling bacteria to steal iron from normally inaccessible transferrin or lactoferrin (Freestone et al, 2000(Freestone et al, , 2007a(Freestone et al, , 2007b(Freestone et al, and 2008Roberts et al, 2002 andArmstrong, 2006 and. Iron is essential for growth of all bacterial pathogens, and its limitation in blood and mucosal secretions via its sequestration by transferrin and lactoferrin is one of the most important innate immune defences against infection (Ratledge and Dover, 2000). Catecholamines, therefore enable bacterial pathogens that lack specific acquisition systems for transferrin and lactoferrincomplexed Fe to acquire the iron needed growth in vivo.…”

Altered desferrioxamine-mediated iron utilization is a common trait of bald mutants of Streptomyces coelicolor

“…2 Iron plays essential roles in house-keeping functions such as DNA replication, protein synthesis and respiration, and siderophore-mediated iron uptake is specifically associated with many other biological processes such as fungal sexual development 3 and germination, 4 plant growth promotion, 5 pilus formation, 6 and pathogen virulence. 7,8 In a study by Ueda and colleagues on terrestrial antibiotic-producing streptomycetes, it was reported that morphological development (e.g. formation of aerial hyphae and spores) and secondary metabolite production was triggered in certain species when they were grown in proximity to isolates producing siderophores (more precisely desferrioxamine E, DFOE).…”