Siderophores

Siderophores

Low-molecular-mass molecules that have a high specificity for chelating or binding iron. Siderophores are produced by many microorganisms, including bacteria, yeast, and fungi, to obtain iron from the environment. More than 500 different siderophores have been identified from microorganisms. Some bacteria produce more than one type of siderophore. See Bacteria, Fungi, Yeast

Iron is required by aerobic bacteria and other living organisms for a variety of biochemical reactions in the cell. Although iron is the fourth most abundant element in the Earth's crust, it is not readily available to bacteria. Iron is found in nature mostly as insoluble precipitates that are part of hydroxide polymers. Bacteria living in the soil or water must have a mechanism to solubilize iron from these precipitates in order to assimilate iron from the environment. Iron is also not freely available in humans and other mammals. Most iron is found intracellularly in heme proteins and ferritin, an iron storage compound. Iron outside cells is tightly bound to proteins. Therefore, bacteria that grow in humans or other animals and cause infections must have a mechanism to remove iron from these proteins and use it for their own energy and growth needs. Siderophores have a very high affinity for iron and are able to solubilize and transport ferric iron (Fe³⁺) in the environment and also to compete for iron with mammalian proteins such as transferrin and lactoferrin. The majority of bacteria and fungi use siderophores to solubilize and transport iron. Microorganisms can use either siderophores produced by themselves or siderophores produced by other microorganisms. See Iron metabolism

The many different types of siderophores can generally be classified into two structural groups, hydroxamates and catecholate compounds. Despite their structural differences, all form an octahedral complex with six binding coordinates for Fe³⁺.

Siderophores have potential applications in the treatment of some human diseases and infections. Some siderophores are used therapeutically to treat chronic or acute iron overload conditions in order to prevent iron toxicity in humans. Individuals who have defects in blood cell production or who receive multiple transfusions can sometimes have too much free iron in the body. However, in order to prevent infection during treatment for iron overload, it is important to use siderophores that cannot be used by bacterial pathogens.

A second clinical application of siderophores is in antibiotic delivery to bacteria. Some gram-negative bacteria are resistant to antibiotics because they are too big to diffuse through the outer-membrane porins. However, siderophore-antibiotic combination compounds have been synthesized that can be transported into the cell using the siderophore receptor. See Antibiotic, Drug resistance