Microorganisms, iron transport

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... 

V. Rdmheld, Existence of two different strategies for the acquisition of iron in higher plants. Iron Transport in Animals. Plants, and Microorganisms (G. Winkel-mann, D. Van der Helm, and J. B. Neilands, eds.), VCH Chemie, Weinheim, Germany, 1987, pp. 353-374. 

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. 

Iron transport agents may belong to the protein or non-protein class. In the former group are found the animal proteins transferrin (25), lactoferrin (26) and conalbumin (27). The low molecular weight iron carrying compounds from microorganisms, the siderochromes, may occur with or without a bound metal ion. Typically, severe repression of biosynthesis of these substances can be expected to set in at an iron concentration of ca. 2 x 10-5 g atoms/liter (28). Most, but not all, of these substances can be described as phenolates or hydroxamates (4). 

Pattus F, Abdallah MA (2000) Siderophores and Iron-transport in Microorganisms. J Chin Chem Soc 47 1... 

Compounds 146-149 were examined for their iron-transport properties in a series of microorganisms including P. agglomerans, Hafnia and E. coli. All compounds were active however, they behaved as fenioxamine in H. alvi, as coprogen in E. coli and both as ferrioxamine and coprogen in P. agglomerans . In order to increase the differential... 

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. 

The siderophores have been discussed in Chapter 22 (Volume 2) and so will only be considered briefly here. All aspects of iron transport in microorganisms and clinical uses of siderophores have been reviewed on many occasions.1169,1170,n72"117 ... 

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. 

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...

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

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). 

Hudson R. J. M. and Morel F. M. M. (1990) Iron transport in marine phytoplankton kinetics of cellular and medium coordination reactions. Limnol. Oceanogr. 35, 1002-1020. Hudson R. J. M. and Morel F. M. M. (1993) Trace metal transport by marine microorganisms implications of metal coordination kinetics. Deep-Sea Res. 40, 129-150. 

Microbial iron transport and infections in animals and plants The Storage of Iron in Microorganisms... 

Since there are some naturally-occurring antibiotics such as the albomycins, which contain the structural features of the siderophores with an appended antibiotic functional unit61,62, synthetic or derivative siderophores may be important new antibiotics 63). In principle these are very effective, since the siderophore antibiotics are recognized as species-generated iron transport agents at the membrane receptor site of producing microorganisms 64). 

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],... 

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