Siderophores Gram-negative bacteria

The Fur protein regulates iron uptake systems in many Gram-negative bacteria. The striking phenotype of the first fur mutants isolated was the overexpression of the outer membrane receptors for siderophore iron transport. In addition, excretion of siderophores under iron-rich growth conditions was observed in these mutants, indicating that the biosynthesis of siderophores is also regulated by Fur. 

Specific receptors for siderophores and vitamin B12 have been identified in the OM of Gram-negative bacteria. The translocation of these ligands across the outer membrane follows an energy-dependent mechanism and also involves the TonB, ExbB, ExbD proteins anchored in the cytoplasmic membrane. Biochemical and genetic data indicate that these proteins form a functional unit (the Ton complex), which couples the outer membrane receptor-mediated... 

Figure 10. Schematic view of the uptake of ferric siderophores by Gram-positive and Gram-negative bacteria. Please note that the murein (peptidoglycan) network associated with the cytoplasmic membrane is not shown. For details see text...

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 ... 

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. 

Gomez JDF, Sansom MSP. Acquisition of siderophores in gram negative bacteria. Nature Rev Mol Cell Biol 2003 4 105-116. 

In Gram-negative bacteria, iron uptake is a complex process because siderophore uptake systems must facilitate... 

Figure 2 Siderophore-mediated iron-uptake systems in E. coli. Siderophore-iron complexes bind to transporter proteins located in the outer membrane (also known as OM), a barrier that is characteristic of Gram-negative bacteria. The region between the outer and inner is known as the periplasmic space. Specific carrier proteins such as FhuD transport iron fi om the outer membrane to the inner or cytosolic membrane (also known as CM). The TonB/ExbB/ExbD complex spans the inner and outer membranes and interacts with FepA, as shown, as well as all of the outer membrane receptors. The linkage that the TonB/ExbB/ExbD complex provides between the inner or cytosolic membrane to the outer membrane is thought to allow transmission of sufficient energy from the cytosol to drive siderophore-iron uptake across the outer membrane...

Bacteria without an OM, such as Gram-positives, do not rely on OM receptors or periplasmic binding proteins for siderophore uptake. Instead, extracellular ferric siderophores are bound by CM-anchored binding proteins that are similar to the periplasmic binding proteins, which then interact with ABC-type transport complexes similar to those employed by Gram-negative bacteria. Once internalized, iron is released from ferric siderophores by the activities of specific cytosolic esterases or reductases. 

Iron uptake from transferrin, siderophores, and haem by Gram-negative bacteria is represented schematically in Fig. 7.5. AU three iron uptake pathways require an outer-membrane receptor, a periplasmic-binding protein (PBP), and an inner-membrane ATP-binding cassette (ABC) transporter. Whereas Fe " -siderophores and haem... 

Transport systems for iron from siderophores, haem, or transferrin in Gram-positive bacteria, which lack an outer membrane, closely resemble the ABC transport systems found in the inner membrane of Gram-negative bacteria. Iron uptake involves a membrane-anchored binding protein, which resembles the PBP of Gram-negative organisms, and a membrane-associated ABC transporter (Fig. 7.9). 

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