Iron-siderophore complex transport bacteria

Most bacteria have the ability to produce and secrete molecules—called siderophores—to fulfill their iron requirements. Siderophores are special iron-chelating agents that facilitate iron solubilization and uptake. They are water-soluble, low-molecular weight molecules that bind ferric ions strongly. The ability of bacteria to utilize siderophores is associated with the presence of transport systems that can recognize and mediate uptake of the ferric-siderophore complexes into the cell. These iron-acquisition systems are regulated in response to iron availability, and their action thus increases under iron limitation conditions. 

In times of iron deficiency, many bacteria and fungi release low molecular weight chelators called siderophores (see Iron Transport Siderophores). These molecules bind ferric iron tightly and the ferric-siderophore complexes are then transported into the cell by a system of uptake proteins. The first stage in the uptake process involves an outer membrane receptor specific to each siderophore. One of the best characterized of these receptors is FhuA, the ferrichrome uptake receptor of E. coli, and we will describe this in detail. However, though other ferric-siderophore complexes are taken up by cells, and their iron released by systems similar to those of ferrichrome, their mechanisms may vary from those of ferrichrome in some respects. FepA and FecA" are two of the outer membrane ferric-siderophore receptors that have recently been structurally characterized. 

The uptake of siderophore-iron complexes by Gram-negative bacteria is energy dependent and occurs via specific outer membrane proteins. In the periplasmic space, it binds to its cognate periplasmic binding protein and is then actively transported across the cytoplasmic membrane by an ATP-trans-porter protein. Three principal mechanisms for transport through the outer membrane have been described ... 

Vanadium, as V0S04, has been found to interfere with siderophore-mediated iron transport in bacteria and plants. This seems to imply that vanadium can be transported by siderophores, and a number of studies focussing on applications of hydroxamate V-complexes in biology have been initiated. 

When deficient in iron, bacteria and fungi produce and excrete to the extracellular medium low molecular weight, specific iron-carrier molecules, called siderophores. These siderophores bind ferric ions, to form soluble complexes. The complexed ferric ions are transported into the cell through high-affinity and energy-dependent receptor proteins located on the outer membrane. In Gram-negative bacteria, such as E. coli, the most studied system, siderophore-iron complexes are transported initially to the periplasm. 

Once the siderophore-iron complexes are inside the bacteria, the iron is released and utilized for vital cell functions. The iron-free hydroxamate siderophores are commonly re-excreted to bring in an additional iron load (Enterobactin is at least partially degraded by a cytoplasmic esterase This cycle is repeated until specific intracellular ferric uptake regulation proteins (Fur proteins) bind iron, and signal that the intracellular iron level is satisfactory, at -which point ne-w siderophore and siderophore-receptor biosynthesis are halted and the iron-uptake process stops. This intricate feedback mechanism allows a meticulous control over iron(III) uptake and accumulation against an unfavorable concentration gradient so as to maintain the intracellular iron(III) level within the required narrow window. Several excellent reviews concerning siderophore-iron transport mechanisms have been recently published i.3,i6, is,40,45,60-62 ... 

Siderophores. If a suitably high content of iron (e.g., 50 pM or more for E. coli) is maintained in the external medium, bacteria and other microorganisms have little problem with uptake of iron. However, when the external iron concentration is low, special compounds called siderophores are utilized to render the iron more soluble.7 11 For example, at iron concentrations below 2 pM, E. coli and other enterobacteria secrete large amounts of enterobactin (Fig. 16-1). The stable Fe3+-enterobactin complex is taken up by a transport system that involves receptors on the outer bacterial membrane.9 12 13 Siderophores from many bacteria have in common with enterobactin the presence of catechol (orftzo-dihydroxybenzene) groups... 

Iron transporters known as siderophores occur in various bacteria. They coordinate iron in a complex that involves three catechol residues. A natural host molecule called entero-bactin is shown along with a cryptand-like molecule (9) that is one of several that were devised to mimic this complexation behavior (reviewed in Roosen-berg, 2000 Raymond, 2003). The catechols deprotonate to the catecholate anions, which provide six oxygen donors for ferric ion The host thus completely envelops the cation permitting transport as the complex. 

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