Disease relevance of Yersiniabactin

• Yersiniabactin (Ybt) synthetase is a three-subunit, 17-domain [7 domains in high molecular weight protein (HMWP)2, 9 in HMWP1, and 1 in YbtE] enzyme producing the virulence-conferring siderophore yersiniabactin in Yersinia pestis [1].
• Growth support by yersiniabactin under iron-restricted conditions was TonB- and Irp65-dependent and correlated with pesticin-sensitivity of Yersinia enterocolitica and Escherichia coli O [2].
• One requirement for the pathogenesis of Yersinia pestis, the causative agent of bubonic plague, is the yersiniabactin (Ybt) siderophore-dependent iron transport system that is encoded within a high-pathogenicity island (HPI) within the pgm locus of the Y. pestis chromosome [3].
• Yersiniabactin production by Pseudomonas syringae and Escherichia coli, and description of a second yersiniabactin locus evolutionary group [4].
• Three similarly divergent yersiniabactin locus groups were determined: the Yersinia pestis group, the P. syringae group, and the Photorhabdus luminescens group; yersiniabactin locus organization is similar in P. syringae and P. luminescens [4].

High impact information on Yersiniabactin

• Purification, priming, and catalytic acylation of carrier protein domains in the polyketide synthase and nonribosomal peptidyl synthetase modules of the HMWP1 subunit of yersiniabactin synthetase [5].
• Acyl-CoA hydrolysis by the high molecular weight protein 1 subunit of yersiniabactin synthetase: mutational evidence for a cascade of four acyl-enzyme intermediates during hydrolytic editing [1].
• Monitoring multiple active sites on thiotemplate enzymes in parallel: a molecular movie of yersiniabactin bioassembly [6].
• A PAI called high-pathogenicity island (HPI) carrying genes involved in siderophore-mediated iron acquisition (yersiniabactin system) has previously been identified in Yersinia pestis, Y. pseudotuberculosis and Y. enterocolitica IB strains, and has been characterized as an essential virulence factor in these species [7].
• C-methyltransferase and cyclization domain activity at the intraprotein PK/NRP switch point of yersiniabactin synthetase [8].

Chemical compound and disease context of Yersiniabactin

• The salicylate synthase, Irp9, from Yersinia enterocolitica is involved in the biosynthesis of the siderophore yersiniabactin [9].
• The HMWP2 subunit of yersiniabactin (Ybt) synthetase, a 230 kDa nonribosomal peptide synthetase (NRPS) making the N-terminus of the Ybt siderophore of Yersinia pestis, has one cysteine-specific adenylation (A) domain, three carrier protein domains (ArCP, PCP1, PCP2), and two heterocyclization domains (Cy1, Cy2) [10].
• Environmental factors influence the production of enterobactin, salmochelin, aerobactin, and yersiniabactin in Escherichia coli strain Nissle 1917 [11].
• The probiotic Escherichia coli strain Nissle 1917 produces four siderophores: the catecholates enterobactin and salmochelin, the hydroxamate aerobactin, and the mixed-type siderophore yersiniabactin [11].
• In Escherichia coli, five chorismate-utilizing enzymes catalyse the synthesis of aromatic compounds such as L-phenylalanine, L-tyrosine, L-tryptophan, folate, ubiquinone and siderophores such as yersiniabactin and enterobactin [12].

Biological context of Yersiniabactin

• Moreover, by complementation of the WA fyuA mutant by the cloned fyuA gene, yersiniabactin uptake and mouse virulence were restored [13].
• Yersinia pestis, the causative agent of plague, makes a siderophore termed yersiniabactin (Ybt), which it uses to obtain iron during growth at 37 degrees C. The genes required for the synthesis and utilization of Ybt are located within a large, unstable region of the Y. pestis chromosome called the pgm locus [14].
• Iron acquisition in plague: modular logic in enzymatic biogenesis of yersiniabactin by Yersinia pestis [15].
• The mycobactin gene cluster has organizational homologies to the yersiniabactin and enterobactin synthetase genes [16].
• We have studied the expression of the fyuA gene, which encodes the outer membrane receptor for the siderophore yersiniabactin (Ybt), and the hemR gene, which encodes the receptor for heme, using the reporter genes gfp (encoding green fluorescent protein) and luc (encoding firefly luciferase) [17].

Associations of Yersiniabactin with other chemical compounds

• Yersiniabactin and salmochelin were maximally produced under neutral to alkaline conditions (pH 7.0 and 7.6, respectively), whereas aerobactin was maximally produced at a more acidic pH (pH 5.6), which agrees with the slightly higher complex stability of hydroxamates at acidic pH values compared to the catecholates [11].
• Yersiniabactin production was also higher with glycerol as the carbon source at pH 7 [11].

Gene context of Yersiniabactin

• HPLC-proven yersiniabactin-producing E. coli lacked modifications found in irp1 and irp2 in the human pathogen CFT073, and it is not clear whether CFT073 produces yersiniabactin [4].
• Compared with probe hybridization, the PCR assay's specificity was 100% and sensitivity 97.1%. fyuA (yersiniabactin: overall prevalence, 93%), traT (serum resistance, 68%), and a pathogenicity-associated island marker (71%) occurred in most strains from both compromised and noncompromised hosts [18].
• CONCLUSIONS: The HMWP1 and HMWP2 domain organization suggests that the yersiniabactin siderophore is assembled in a modular fashion, in which a series of covalent intermediates are passed from the amino terminus of HMWP2 to the carboxyl terminus of HMWP1 [15].
• Mutating ybtS revealed that this gene encodes a protein essential for yersiniabactin synthesis [15].
• Polypeptides encoded by the fyuA gene located on the HPI could be detected by using immunoblot analysis in most of the HPI-positive STEC strains, suggesting the presence of a functional yersiniabactin system [19].

Analytical, diagnostic and therapeutic context of Yersiniabactin

• The production of the siderophore yersiniabactin was also demonstrated in these HPI-positive strains by use of a reporter gene bioassay [20].

References