Disease relevance of C05554

• Aerobactin-mediated iron uptake: a virulence determinant in enteropathogenic Escherichia coli [1]?
• The aerobactin iron transport system genes in Shigella flexneri are present within a pathogenicity island [2].
• The presence of the aerobactin genes on plasmids in E. coli pColV and Salmonella, on a pathogenicity island in S. flexneri and S. sonnei and in a different chromosomal location in S. boydii and some E. coli suggests that these virulence-enhancing genes are mobile, and they may constitute an island within an island in S. flexneri [2].
• A competitive enzyme-linked immunosorbent assay with MAb AERO1 had a limit of 10 nM for the detection of purified ferric aerobactin and allowed detection of the crude aerobactin produced by various members of the family Enterobacteriaceae isolated from cancer patients with bacteremia [3].
• In contrast, aerobactin synthesis was rare (3%), with isolates from pyelonephritis showing the highest frequency of aerobactin production (3/19) [4].

High impact information on C05554

• In vitro Fur DNA-binding activity, as measured by protection of restriction site in aerobactin promoter, is directly sensitive to NO [5].
• Dark-field electron microscopy of positively stained Fur-DNA complexes in addition to atomic force microscopy allowed direct visualization of Fur interactions with the regulatory regions of aerobactin and hemolysin operons and provided complementary information about the structure of the complexes [6].
• Virulence factors of recognized importance in the pathogenesis of urinary tract infection (UTI) include adhesins (P fimbriae, certain other mannose-resistant adhesins, and type 1 fimbriae), the aerobactin system, hemolysin, K capsule, and resistance to serum killing [7].
• Production of the siderophore aerobactin in Escherichia coli is transcriptionally metalloregulated through the iron-dependent binding of the Fur (ferric uptake regulator) to a large region (>100 base pairs) within the cognate promoter in the pColV-K30 plasmid [8].
• Evidence of an unusually long operator for the fur repressor in the aerobactin promoter of Escherichia coli [8].

Chemical compound and disease context of C05554

• These results may help to explain why production of aerobactin, despite its relatively low affinity for iron, is more closely associated with invasiveness in E. coli than is enterochelin production [9].
• 1. The enzyme shows approximately 50% homology with functional analogs, i.e., L-lysine N6-hydroxylase of aerobactin-producing Escherichia coli and L-Orn N5-oxygenase of ferrichrome-producing Ustilago maydis [10].
• Complementation analyses and identification of aerobactin precursors accumulated by Escherichia coli cells harboring the different constructions allowed assignment of the iucA and iucC genes to discrete steps in biosynthesis of the siderophore from N epsilon-acetyl-N epsilon-hydroxylysine and citrate [11].
• Each of the four hydroxamate compounds, ferrichrome, aerobactin, rhodotorulic acid, and coprogen, known to transport ferric iron into Escherichia coli requires a specific outer membrane receptor protein [12].
• E. coli with type I pili aspirated from augmented rats and three clinically isolated strains of E. coli, C5 (type I pili, aerobactin), C92 (type I pili, aerobactin, P fimbriae), and C189 (type I pili, aerobactin, P fimbriae, CNF), were transurethrally inoculated into the augmented bladder of rats [13].

Biological context of C05554

• In the presence of a divalent metal, such as Mn2+, the Fur protein sequentially occupies two defined sites at the aerobactin promoter region, followed by a looser occupation of upstream DNA sequences [14].
• Metal ion regulation of gene expression. Fur repressor-operator interaction at the promoter region of the aerobactin system of pColV-K30 [15].
• The genes iucA and iucC, which determine the two subunits of the aerobactin synthetase complex, showed a considerable homology within three stretches of their amino acid sequence [16].
• The region includes five open reading frames which correspond to the genes iucA, iucB, iucC and iucD, encoding the enzymes of the biosynthetic pathway for aerobactin, and iutA for the outer membrane receptor of ferri-aerobactin complexes [16].
• Phenotypic characterization of the prototype EAF plasmid pMAR2 reveals that the plasmid belongs to the group IncFII and is negative for alpha-hemolysin, colicin, and aerobactin synthesis, as well as biochemical markers and antibiotic resistance [17].

Anatomical context of C05554

• The Iut- mutant was found in smaller numbers in the duodenum, suggesting that aerobactin conferred a significant selective advantage for colonization of this intestinal segment [18].
• In rats with negative urine culture after augmentation experimental cystitis was induced by the transurethral inoculation of E. coli C5, with type I pili and aerobactin or E. coli C92 with type I pili, P fimbriae and aerobactin at a concentration of 10(5) colony forming units per 0.3 ml [19].
• One of these proteins, IucD439, was purified to homogeneity from the soluble fraction of the cell lysates, and it was capable of participating in the biosynthesis of aerobactin, as determined in vitro by a cell-free system and in vivo by a cross-feeding bioassay [20].
• The characteristics exhibited by virulent strains were invasion for HeLa and chicken fibroblast cells, serum resistance, colicin V, and aerobactin production [21].
• All samples except the last cervix swab contained isolates of serotype O12:K1:H7, which produced adhesins, P fimbriae, type I fimbriae and the iron-chelator aerobactin [22].

Associations of C05554 with other chemical compounds

• In support of this notion we demonstrate specific binding of the Fe3+ hydroxamate compounds ferrichrome, aerobactin, and coprogen, which are transported via the Fhu system, to the periplasmic FhuD protein, and no binding of the transport inactive ferrichrome A, ferric citrate, and iron sulfate [23].
• The results of bioassays and DNA-DNA hybridization experiments indicated that pathogenic strains of S. typhi produced enterochelin but not aerobactin [24].
• The effect of serum and serum proteins on enterobactin- and aerobactin-mediated utilization of transferrin iron has been investigated [25].
• Certain of the newly detected VF genes, e.g., fyuA (yersiniabactin; 76%) and focG (F1C fimbriae; 25%), were as prevalent or more prevalent than their more familiar traditional counterparts, e.g., iut (aerobactin; 57%) and sfaS (S fimbriae; 14%), thus possibly offering additional useful targets for preventive interventions [26].
• Virulence factors associated with APEC include type 1 and P fimbriae, curli, aerobactin, lipopolysaccharide (LPS), K1 capsular antigen, temperature-sensitive hemagglutinin (Tsh), and an uncharacterized pathogen-specific chromosomal region (the 0-min region) [27].

Gene context of C05554

• A strain of E. coli bearing a lacZ fusion to the aerobactin operon was used to compare the metal specificities of the regulation of MnSOD and of aerobactin by Fur [28].
• Differential regulation of the genetic determinants of the two siderophores resulted in preferential induction of the aerobactin system in the presence of unsaturated levels of transferrin and lactoferrin [29].
• Only the wild-type, aerobactin-producing strain could remove iron from transferrin or lactoferrin [30].
• The virulence genes found were: fim in all eight isolates, csgA in seven, aer in six, and pap, crl and tsh in one isolate each [31].
• No correlation was found between the fimH and fimA sequences and the following parameters: avian species, organ of isolation, serotype, presence of aerobactin receptor and virulence for chickens [32].

Analytical, diagnostic and therapeutic context of C05554

• Polymerase chain reaction and Southern hybridization data indicate that SHI-2 is present in the same location in Shigella sonnei, but the aerobactin genes are not located within SHI-2 in Shigella boydii or enteroinvasive E. coli [2].
• This strain exhibited a functional aerobactin-mediated iron uptake system, as assessed by a cross-feeding bioassay and by its sensitivity to cloacin, a bacteriocin that recognizes the outer membrane receptor for iron-aerobactin complexes [33].
• A sequence analysis of the DNA at the junction of the first and second genes in the aerobactin operon, considered in conjunction with the N-terminal amino acid sequence of the isolated protein, enabled the conclusion that the acetylase is specified by the second gene in the complex [34].
• Aerobactin was identified by electrophoretic mobility, spectrophotometric titration, proton nuclear magnetic resonance spectroscopy, mass spectrometry, acid hydrolysis, and biological activity [35].
• However, both the nuclear magnetic resonance spectrum and fast-atom bombardment mass spectrometry of the siderophore purified from EK33 confirmed its identity with aerobactin [36].

References