Disease relevance of Anguibactin

• Sequence analysis followed by homology studies indicated that transport of ferric anguibactin into Vibrio anguillarum 775 follows the same mechanism as reported for transport of Fe(3+)-hydroxamates, Fe(3+)-catecholates, ferric dicitrate, and vitamin B12 into Escherichia coli [1].
• FcuA shared 34.6% amino acid sequence homology with FatA, the anguibactin receptor of Vibrio anguillarum, but only 20.6% homology with FhuA, the ferrichrome receptor of E. coli [2].
• The Acinetobacter baumannii 19606 prototype strain produces a 78-kDa iron-regulated outer membrane protein immunologically related to FatA, which is required for iron acquisition by the fish pathogen Vibrio anguillarum via the anguibactin-mediated system [3].

High impact information on Anguibactin

• According to their homologies to other proteins from other transport systems, they may be involved in the translocation of ferric anguibactin across the cytoplasmic membrane [1].
• A high homology in the primary structure of FatB to FhuD, FecB, FepB, and BtuE suggests that FatB is the anguibactin-binding protein located in the periplasmic space [1].
• Five open-reading frames have been identified, one of which encodes the outer membrane receptor for ferric anguibactin, OM2 [4].
• In addition, we present evidence that anguibactin itself enhanced transcription of the iron-transport genes fatA and fatB, independently of AngR and the trans-acting factor (TAF) product(s) [5].
• Vibrio anguillarum virulence is associated with the presence of a plasmid-mediated iron-uptake system expressed under iron-limiting conditions, which consists of the siderophore anguibactin and specific iron-transport proteins [5].

Chemical compound and disease context of Anguibactin

• A histidine decarboxylase gene encoded by the Vibrio anguillarum plasmid pJM1 is essential for virulence: histamine is a precursor in the biosynthesis of anguibactin [6].
• Chromosome-mediated 2,3-dihydroxybenzoic acid is a precursor in the biosynthesis of the plasmid-mediated siderophore anguibactin in Vibrio anguillarum [7].
• Some of the strains also promoted the growth of S. typhimurium enb-1 (which can use only enterobactin as a siderophore) as well as some strains of Vibrio anguillarum deficient in the anguibactin-mediated system [8].
• Acinetobactin was structurally related to anguibactin, a plasmid-encoded siderophore of Vibrio anguillarum [9].

Biological context of Anguibactin

• We have identified and sequenced an hdc gene in the Vibrio anguillarum plasmid pJM1 which encodes a histidine decarboxylase enzyme and is an essential component for the biosynthesis of anguibactin [6].
• In order to dissect the specific domains of AngR associated with regulation of iron transport gene expression, anguibactin production, and virulence, we also generated a panel of site-directed angR mutants, as well as deletion derivatives [10].
• Insertions in the remaining genetic unit led to an iron uptake-deficient phenotype and showed either reduced levels of the outer membrane protein OM2 as well as anguibactin activity or a complet shutoff of both OM2 and anguibactin biosyntheses [11].
• We report the identification of a novel chromosome cluster of genes in Vibrio anguillarum 775 that includes redundant functional homologues of the pJM1 plasmid-harbored genes angE and angC that are involved in anguibactin biosynthesis [12].
• The results of site-directed mutagenesis and in vivo phosphorylation experiments suggest that the carboxy-terminal end of AngB and the AngG polypeptide(s) function as aryl carrier proteins involved in the assembly of the anguibactin molecule [13].

Anatomical context of Anguibactin

• A subset of these proteins are involved in the biosynthesis of the siderophore anguibactin and in the internalization of the ferric-siderophore into the cell cytosol [14].

Associations of Anguibactin with other chemical compounds

• The role of histidine decarboxylase in biosynthesis of anguibactin was confirmed by the fact that growth under iron starvation was restored by addition of histamine to the medium [6].
• Thus, our results in this work demonstrate that the lipopolysaccharide O1 side chain is required for the operation of two critical virulence factors in V. anguillarum: serum resistance and anguibactin-mediated iron transport [15].
• The plasmid pJM1 confers on V. anguillarum the ability to take up ferric iron as a complex with anguibactin from a medium in which iron is chelated by transferrin, ethylenediamine-di(o-hydroxyphenyl-acetic acid), or other iron-chelating compounds [16].
• Substitution by alanine of the serine 215 in the PCP domain and of histidine 406 in the C domain of AngM results in an anguibactin-deficient phenotype, underscoring the importance of these two domains in the function of this protein [17].
• These protein similarities, as well as the structural similarity of anguibactin and acinetobactin, suggested that these two siderophores could be utilized by both bacterial strains, a possibility that was confirmed by siderophore utilization bioassays [18].

Gene context of Anguibactin

• The angR locus in Vibrio anguillarum encodes a trans-acting transcriptional activator which modulates several Fe2(+)-regulated loci in the anguibactin biosynthesis gene cluster [19].
• We also show in this study that the angT gene, found downstream of angR, intervenes in the mechanism of anguibactin production but is not essential for virulence or iron transport gene expression [10].
• The mutations in angM that affected anguibactin production also resulted in a dramatic attenuation of the virulence of V. anguillarum 775, highlighting the importance of this gene in the establishment of a septicemic infection in the vertebrate host [17].
• Irp4 was found to have 41.7% similarity to thioesterase-like protein of the anguibactin biosynthetic genes of Vibrio anguillarum [20].
• The siderophore anguibactin is not utilized as an external siderophore, and although characteristic outer membrane proteins are synthesized under iron-limiting conditions, these are not related to the plasmid-mediated outer membrane protein OM2 associated with ferric anguibactin transport [21].

Analytical, diagnostic and therapeutic context of Anguibactin

• Our bioassay and complementation experiments with this mutant demonstrate that the chromosome-mediated 2,3-DHBA is a precursor of the pJM1 plasmid-mediated siderophore anguibactin [7].
• Molecular cloning of pJM1 plasmid DNA noncontiguous to the iron uptake region also identified genetic determinants for a trans-acting factor required for full expression of anguibactin activity [11].

References