Siderophore - Defination, Secretion, Types, Applications & Examples

 

 Siderophores are High affinity iron chelating compounds. Siderophores are small, low molecular weight molecules (500-1000 Daltons). Siderophores are produced by bacteria, fungi, cyanobacteria, and plants, growing at a low Fe3+ concentration. Siderophores are produced and secreted by microorganisms in order to mediate the uptake of essential iron into the cell.

Siderophores Secretion :

  Iron is essential for all living organisms, as it is involved in a various metabolic pathways.
  The aerobic atmosphere of the planet has caused the surface iron to oxidized to insoluble hydroxide polymer and reduce the level of free iron, so microorganism use such systems for sufficient uptake from their environment.
  Siderophore-iron complexes are transported into the cell through receptors in the membrane, these molecules are encoded by five genes in operon which is turned off when sufficient iron has been taken into the cell.
  In Gram positive bacterial species, a putative cell surface lipoprotein receptor anchored in the cytoplasmic membrane through its N-terminal lipid moiety and an ABC-type transporter are required for the transport of the siderophore-iron complex.
  Siderophores, along with other iron acquisition systems, are virulence factors in many bacterial pathogens.

Examples

- Pseudomonas (very active siderophore producer)   
- Azotobacter Bacillus
- Streptomyces
- Serratia Enterobacter
- Azospirillum Rhizobium

Types of Siderophores

1). Hydroxamate siderophore :

• Hydroxamate siderophores are Produced by bacteria and fungi.
• Most groups, C(=0)N-COH)R where R is an amino acid or derivative.
• Each hydroxamate group provides two oxygen molecules, which form a bidentate ligand with iron. Therefore, each siderophore forms a hexadentate octahedral complex with Fe3+.
• Hydroxamate siderophores usually show strong absorption between 425 and 500 nm when bound to iron.
Ferrichrome produced by the fungus Ustilago sphaerogena. Ferribactin produced by Pseudomonas fluorescens is known to be a hydroxamate.
Gonobactin and Nocobactin produced in small quantities by Neisseria gonorrhoeae and N. meningitids are also hydroxamates.

2). Catecholate (Phenolates) siderophore :

•  Enterochelin the cyclic trimester of 2, 3- dihydroxybenzoylserine, is produced by E. coli, S. typhimurium and K. pneumonia and is the prototype of the catecholate siderophore.
•  Each catecholate group provides two oxygen atoms for chelation with iron so that a hexadentate octahedral complex is formed as in the case of the hydroxamate siderophores.
•  Agrobactin and parabactin are produced by Agrobacterium tumefaciens and Paracoccus denitrificans.
•  Erwinia carotovora produced catecholates while Pseudomonas produced a mixed catecholate- hydroxamate siderophore.

3). Carboxylate (complexones) siderophore :

• The best characterized carboxylate type siderophore with a novel structure is Rhizobactin.
• Rhizobactin is produced by Rhizobium meliloti strain DM4 and is an amino poly (carboxylic acid) with ethylenediaminedicarboxyl and hydroxycarboxyl moieties as ironchelating groups.
• Staphyloferrin A, produced by Staphylococcus hyicus DSM20459, is another member of this class of complexon siderophores.
•  These are known to be amino polymers of carboxylic acid.

Examples of Microorganisms with Siderophores Produced
Microorganisms Siderophore
Ustilago sphaerogena Ferrichrome   
Streptomyces pilosus Desferrioxamines
Escherichia coli Enterobactin
Aeromonas hydrophila Amonabactin
Aerobacter aerogens,
Salmonella sp,
Klebsiella pneumonia
Aerobactin
Vibrio cholerae Marine
V. anguillarum Anguibactin
Acenetobacter calcoaceticus Acinetobactin
Mycobacterium tuberculosis Mycobactin
Pseudomonas aeruginosa  Pyoverdin
Yersinia pestis Yersiniabactin

Application of Siderophore :

Sideromycin

• Sideromycins are iron-chelating antibiotics produced by Streptomyces.
• Albomycin and ferrimycin are two examples of this group being closely related to ferrichrome. Both antibiotics contain an extra chemical group attached to the basic siderophore structure.
•  Thus, they use the siderophore transport system to gain access to the cell, but once inside the cell their mechanism of action is not against iron transport or its acquisition. Instead these antibiotics exert their effect by inhibiting protein synthesis, similar to many other antibiotics.
•  When the functional group is removed, the molecules lose their antibiotic activity but their growth promoting activities as siderophores are retained.

Iron overload diseases, β Thalassemia

•  In certain diseases, Periodic whole blood transfusion is required. This leads to steady buildup of iron in body. These conditions and other primary iron overload diseases such as hemochromatosis and hemosiderosis and accidental iron poisoning requires removal of iron from the body, from liver.
•  Such diseases can be efficiently treated with siderophore based drug and siderophore act as principal model.

Iron chelators and cancer

• Siderophores like Dexrazoxane, O-trensox, desferriexochelins, desferrithiocin, tachpyridine have found to be effective in cancer therapy.
•  They are also used for the clearance of non-transferrin bound iron in serum which occurs in cancer therapy as a result of some chemotherapies.

Anti-Malarial

•  Some bacterial siderophores have been found to be useful in the treatment of mlaria caused by Plasmodium falciparum.
• EXAMPLE
   Desferrioxamine-B produced by Streptomyces pilosus is active against P. falciparum.
  Siderophore enters inside P. falciparum cell and causes intracellular iron depletion. Same effect is shown against Trypanosoma brucei which is known for causing sleeping sickness in humans.

Biocontrol agent

•  By producing antibiotics, siderophores and cyanide bacteria suppress the growth of deleterious microorganisms.
•  Siderophores are themselves growth inhibitors of various phytopathogenic fungi, such as Phytophthora parasitica, Phythium ultimum, Fusarium oxysporum and Sclerotinia sclerotiorum.


References:
- Bacterial Siderophore and their Application: A review- Syed Sajeed Ali* and N.N. Vidhale
- Bacterial Siderophores and their Biotechnological applications - C. Mohandass