Disease relevance of Enterochelin

• The activity of an efficient iron uptake process was clearly shown by experiments with a mutant of E. coli deficient in enterochelin biosynthesis [1].
• The immunoglobulin fraction from normal human serum was isolated; when added to a defined medium (M199) prepared so as to mimic normal human serum, the immunoglobulin rendered the medium inhibitory to an enterochelin-defective strain of Salmonella typhimurium [2].
• Subinhibitory MICs (sub-MICs) of several cephalosporins significantly reduced the enterochelin production of Klebsiella pneumoniae 327 grown under iron-depleted conditions and also reduced capsule formation regardless of iron availability [3].
• A number of studies point to the conclusion that enterochelin, the iron chelator produced by a number of pathogenic enterobacteria, may be an essential metabolite for bacterial multiplication within the host [4].
• These findings are consistent with the S. typhi enterochelin system playing a role in the pathogenesis of typhoid fever [5].

High impact information on Enterochelin

• The 195-kDa complex was shown to contain both TonB and FepA, the outer membrane receptor for the siderophore enterochelin [6].
• Cooperative uptake of microcin E492 by receptors FepA, Fiu, and Cir and inhibition by the siderophore enterochelin and its dimeric and trimeric hydrolysis products [7].
• When introduced into an E. coli fepA cir fiu aroB mutant, IroN, but not IroBCDE, mediated the utilization of structurally related catecholate siderophores, including 2,3-dihydroxybenzoyl-L-serine, 2,3-dihydroxybenzoyl-D-ornithine, 2,3-dihydroxybenzoic acid, and enterochelin [8].
• A gene (pldA) encoding a 35.0-kDa protein with significant homology to the Escherichia coli outer membrane phospholipase was identified upstream of an operon encoding an enterochelin transport system in Campylobacter coli [9].
• Iron starvation interferes drastically with the multiplication and virulence of Salmonella typhi mutants defective in enterochelin synthesis or enterochelin transport [5].

Chemical compound and disease context of Enterochelin

• Differences in excretion and efficiency of the aerobactin and enterochelin siderophores in a bovine pathogenic strain of Escherichia coli [10].
• The ability of Salmonella typhimurium to synthesize enterochelin (enterobactin; ENT) affects its capacity to grow both in vivo and in vitro [11].
• Mutants of Escherichia coli K-12 that are unable to make use of the enterochelin transport system were used to confirm that streptonigrin requires iron for its bactericidal action [12].
• Antibacterial effect of scandium and indium complexes of enterochelin on Klebsiella pneumoniae [4].
• A factor produced by Escherichia coli K-12 inhibits the growth of E. coli mutants defective in the cytochrome bd quinol oxidase complex: enterochelin rediscovered [13].

Biological context of Enterochelin

• All isolates produced enterochelin, but only production of aerobactin could be correlated with virulence [14].
• In addition, the presence of plasmid deoxyribonucleic acid in a mutant defective in enterochelin biosynthesis was associated with a marked increase in the rate of radioactive-iron uptake [15].
• Tn5 mutagenesis of the enterochelin gene cluster of Escherichia coli [16].
• The three restriction fragments collectively cover a region of the chromosome 29 kg in length, indicating that the genes of the enterochelin system are clustered but not contiguous [17].
• Insertional mutagenesis of fepD or fes genes abrogates enterochelin-supported growth of Y. enterocolitica on iron-chelated media [18].

Anatomical context of Enterochelin

• Our results demonstrated that, whatever the exogenous iron-chelating agent used, aerobactin was rapidly excreted, whereas enterochelin accumulated early in periplasm before its very belated release into the external medium [10].
• Although aerobactin has a dramatically lower affinity for iron than enterochelin, it has been shown to provide a significant selective advantage for bacterial growth in conditions of iron limitation, such as in the body fluids and tissues of an infected animal [19].
• One of the mutants (cbt) was apparently defective in outer membrane ferri-enterochelin receptor activity. aroE derivatives (unable to synthesize enterochelin) of the four mutant classes and the parent strain produced increased amounts of two outer membranes polypeptides when grown under iron stress [20].
• As in the case of serum, the bacterial iron transporting compound, enterochelin, abolished the bacteriostatic effect of human milk [21].
• The outer membrane isolated from cells grown in the iron-deficient media showed enterochelin-stimulated binding of iron, while the outer membrane from iron-rich cells and cytoplasmic membranes from both types of cells did not show such binding activity [22].

Associations of Enterochelin with other chemical compounds

• This antibody can be isolated from serum by sodium sulfate fractionation or affinity chromatography by employing an enterochelin-derived ligand (2,3-dihydroxy-N-benzoyl-L-serine) attached to aminohexyl Sepharose 4B [23].
• In contrast to transferrin, 2,2'-dipyridyl induced a greater efficiency of enterochelin, possibly by a more permanent function as iron-binding compounds in the bacterial envelope [10].
• Although the presence of the siderophore enterochelin (also known as enterobactin) greatly enhanced detectable cross-linking between TonB and the outer membrane receptor, FepA, the absence of enterochelin did not prevent the localization of TonB to the outer membrane [24].
• Both serine and chorismate are precursors of enterochelin; this may be why serC and aroA are in a single operon [25].
• Identification of high-affinity ligands, bacterial catecholate-type siderophores (such as enterochelin), suggested a possible function for siderocalin: an antibacterial agent, complementing the general antimicrobial innate immune system iron-depletion strategy, sequestering iron as ferric siderophore complexes [26].

Gene context of Enterochelin

• Four of the mutants studied (cbt, exbC, exbB, and tonB) hypersecreted enterochelin [27].
• Mutants in entA or aroB, defective in the production of enterochelin, did not produce the factor that inhibits the growth of cydAB and cydDC mutants; purified enterochelin inhibited the growth of Cyd- mutants, but not that of wild-type cells [13].
• Biosynthesis of enterochelin in Escherichia coli K-12: separation of the polypeptides coded for by the entD, E, F and G genes [28].
• Four enzymic components, coded for by the entD, entE, entF and entG genes, involved in the biosynthesis of enterochelin from 2,3-dihydroxybenzoate have been separated from cell extracts of mutant strains of Escherichia coli K-12 [28].
• We recently demonstrated that enterochelin, a bacterial catecholate siderophore, binds to the host protein lipocalin 2 (ref. 5). Here, we show that this event is pivotal in the innate immune response to bacterial infection [29].

Analytical, diagnostic and therapeutic context of Enterochelin

• All strains produced the iron-scavenging system enterochelin as analyzed by bioassay and DNA hybridization [30].
• The microcin antagonist was identified as enterochelin through thin-layer chromatography [31].
• The addition of excess iron to the medium allows the enterochelin to accumulate as the ferric-enterochelin complex which is purified by ion-exchange chromatography and then dissociated and the free enterochelin further purified by differential extraction and crystallization [32].

References