Microbial Iron Uptake

The use of microbial siderophores by dicotyledonous plants appears to involve uptake of the entire metallated chelate (42-44), or an indirect process in which the siderophore undergoes degradation to release iron (45). As demonstrated in initial studies examining this question, there was concern that iron uptake from microbial siderophores may be an artifact of microbial iron uptake in which radiolabeled iron is accumulated by root-colonizing microorganisms (46). Consequently, evidence for direct uptake of iron from microbial siderophores has required the use of axenic plants. In experiments with cucumber, it was shown that the microbial siderophore ferrioxamine B could be used as an iron source at concentrations as low as 5 pM and that the siderophore itself entered the plant (42). 

B. F. Matzanke, Mossbauer Spectroscopy of Microbial Iron Uptake and Metabolism, in Iron Transport in Microbes, Plants and Animals , eds. G. Winkehnann, D. van der Helm, and J. B. Neilands, VCH, Weinheim, 1987, p. 251. 

The po.ssible role of a chelate reductase for iron uptake from microbial siderophores has been examined for several plant species (30,47). With certain microbial siderophores such as rhizoferrin and rhodotorulic acid, the reductase may easily cleave iron from the siderophore to allow subsequent uptake by the ferrous iron transporter. However, with the hydroxamate siderophore, ferrioxamine B, which is produced by actinomycetes and u.sed by diverse bacteria and fungi, it has been shown that the iron stress-regulated reductase is not capable... 

Iron uptake by bacteria at sites of lateral root emergence has been further confirmed using another technique employing 7-nitrobenz-2-oxa-l,3-diazole-desferrioxamine B, which is a derivitized siderophore that becomes fluorescent after it is deferrated (78). In this case, iron uptake from the siderophore ferrox-amine B was a.ssociated primarily with microbially colonized roots, but both plant and iron uptake from this chelate occurred in the regions just behind the root tips. 

D. E. Crowley. V. Romheld, H. Marschner, and P. J. Szaniszlo. Root-microbial effects on plant iron uptake from siderophores and phytosiderophores. Plant Soil 142 1 (1992). 

E. Bar Ness, Y. Hadar, Y. Chen, and A. Shanzer, Iron uptake by plants from microbial siderophores—a study with 7 nitrobenz-2oxa-1,3-diazole desferrioxamine as fluorescent ferrioxamine B analog. Plant Physiol. 99 1329 (1992). 

Iron homeostasis in mammalian cells is regulated by balancing iron uptake with intracellular storage and utilization. As we will see, this is largely achieved at the level of protein synthesis (translation of mRNA into protein) rather than at the level of transcription (mRNA synthesis), as was the case in microorganisms. This is certainly not unrelated to the fact that not only do microbial cells have a much shorter division time than mammalian cells, but that one consequence of this is that the half-life of microbial mRNAs is very much shorter (typically minutes rather than the hours or often days that we find with mammals). This makes it much easier to control levels of protein expression by changing the rate of specific mRNA synthesis by the use of inducers and repressors. So how do mammalian cells... 

Unlike desferrioxamine analogs designed for specific therapeutic purposes described above, chiral DFO analogs that form conformationally unique complexes with iron(lll) were designed to serve as chemical probes of microbial iron(lll) uptake processes. As mentioned above, ferrioxamine B can form a total of five isomers when binding trivalent metal ions, each as a racemic mixture. Muller and Raymond studied three separate, kinetically inert chromium complexes of desferrioxamine B (N-cis,cis, C-cis,cis and trans isomers), which showed the same inhibition of Fe-ferrioxamine B uptake by Streptomyces pilosus. This result may indicate either that (i) ferrioxamine B receptor in this microorganism does not discriminate between geometrical isomers, or that (ii) ferrioxamine B complexes are conformationally poorly defined and are not optimal to serve as probes. 

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). 

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... 

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