Microorganisms, iron transport systems

Figure 1. Schematic of the two iron transport systems of microorganisms. The high affinity system is comprised of specific carriers of ferric ion (siderophores) and their cognate membrane hound receptors. Both components of the system are regulated by iron repression through a mechanism which is still poorly understood. The high affinity system is invoked only when the available iron supply is limiting otherwise iron enters the cell via a nonspecific, low affinity uptake system. Ferri-chrome apparently delivers its iron by simple reduction. In contrasty the tricatechol siderophore enterobactin may require both reduction and ligand hydrolysis for release...

The stereochemistry of siderophores is a very important aspect of their role in mediated iron uptake, since it has been shown that very subtle discrimination by microbial iron transport systems takes place between siderophore isomers. In fact, uptake of siderophores by microorganisms shows - at least in part - stereospecific preferences (Section 5.2). 

In order to identify a eukaryotic iron transporter, we chose to work with the yeast Saccharomyces cerevisiae because of its tractable genetic system and the simplicity and redundancy of its iron transporters. S. cerevisiae employs two main methods to obtain iron from the environment. One, they possess a siderophore-dependent iron transport system [10]. While S. cerevisiae is able to use siderophores secreted by other microorganisms, it does not make or secrete siderophores [11]. Two, in laboratory conditions S. cerevisiae must rely on elemental iron transport which depends on cell surface ferrireductases to convert extracellular ferric chelates to ferrous iron [12]. Two yeast ferrireductase genes FREl and FRE2 are transcriptionally induced by iron need and have been shown to play a role in iron transport [13, 14]. The ferrireductases possess multiple transmembrane domains and potential FAD and NADPH binding domains. These ferrireductases use intracellular NADPH as an electron donor for the conversion of ferric iron to ferrous (Figure 4-1) [15]. The ferrireductases also require heme biosynthesis for function and bind two heme molecules in a maimer similar to the B-type cytochromes [16],... 

Some natural antibiotics contain a siderophore structure, for instance, 5i-albomycin 35, which is produced by Streptomyces subtropicus. The linear tripeptide portion chelates Fe(III) and, thereby, is able to utilize the iron-transport system of a range of microorganisms. Subsequent to uptake, peptidases localized in the cytoplasmic membrane hydrolytically release the toxic thioribosyl moiety. In principle, this property can be used for selective drug delivery. Preliminary studies indicated that substantial modification of the siderophore framework can be tolerated by microbial iron-transport systems. Surprisingly, simple modifications can be made to cephalosporin molecules, which endow them with the ability to interact with microorganism iron-transport mechanisms. Thus, simple incorporation of a catechol moiety, as in 36, endows this molecule with enhanced activity against Pseudomonas aeruginosa when compared... 

Depending on the ability of specific transport systems to utilize the predominant metal chelates present in the soil solution, competition may occur between plants and microorganisms and between different types of microorganisms for available iron. This has been particularly well studied for Pseudomonas sp., which produce highly unique iron chelators that are utilized in a strain specific manner but which also retain the ability to use more generic siderophores pro-... 

J. B. Neilands, Overview of bacterial iron transport and siderophore systems in rhizobia. Iron Chelation in Plants and Soil Microorganisms (L. L. Barton and B. C. Heming, eds.). Academic Press, London, 1993, pp. 179-195. 

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... 

Mammalian control systems for iron transport are more complex than those found in microorganisms. In both cases, there is the problem that, at physiological pH values, iron will be present as highly insoluble Fenl polymeric species of composition Fe(0)(0H). Organisms need to solubilize iron and to prevent the iron forming insoluble species during storage. 

Price, N. M., and F. M. M. Morel. 1998. Biological cycling of iron in the ocean. In Iron Transport and Storage in Microorganisms Plants and Animals Metal Ions in Biological Systems (A. Sigel and H. Sigel, Eds.), pp. 1-36. Dekker, New York. 

DOM can also act as an electron acceptor for biotically mediated oxidation reactions. Many active microorganisms, particularly phototrophs, produce reductants in excess of metabolic needs that must be regenerated by transfering electrons to acceptors in the environment via membrane-spanning reductases (Price and Morel, 1990). It has been discovered that some iron-reducing bacteria use humic and fulvic acids as terminal electron acceptors for their respiratory transport systems (Coates et al., 1998). 

Biological Systems, vol 35 Iron Transport and Storage in Microorganisms, Plants and Animals. Marcel Dekker, New York, p 239... 

Virtually all microorganisms—with the exception of certain lactobacilli— require iron as cofactor of many metabolic enzymes and regulatory proteins because of its ability to exist in two stable oxidation states. Although iron is one of the most abundant elements in the environment, it is often a limiting factor for bacterial growth. This is so because of the formation of insoluble ferric hydroxide complexes under aerobic conditions at neutral pH, which impose severe restrictions on the availability of the element. Consequently, bacteria have evolved specialized high-affinity transport systems in order to acquire sufficient amounts of this essential element. 

This pathway was first found in microorganisms which produce SA or the related compound 2,3-DHBA. The function of these compounds is different from that in plants. Under aerobic growth conditions, iron occurs in the environment as the highly insoluble Fe(OH)j. To overcome the problem of Fe " deficiency almost all bacteria and fungi have evolved high-affinity Fe transport systems based on the synthesis of low-molecular-mass... 

A. Shanzer and J. Libman, Biomimetic Siderophores from Structural Probes to Diagnostic Tools, in Iron Transport and Storage in Microorganisms, Plants, and Animals , Vol. 35 of Series Metal Ions in Biological Systems, eds. A. Sigel and H. Sigel, Marcel Dekker, Basel, 1998, p. 329. 

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