Functional analysis of yersiniabactin transport genes of Yersinia enterocolitica

Brem, Daniela; Pelludat, Cosima; Rakin, Alexander; Jacobi, Christoph A.; Heesemann, J.

doi:10.1099/00221287-147-5-1115

Cited by 53 publications

(51 citation statements)

References 50 publications

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“…6, right side) has strictly no resemblance with phylogenetic trees based on a sequence comparison of 16 S rRNAs or housekeeping proteins (41), suggesting that the ICS genes have traveled widely in the microbial world. This idea is supported by the finding that the irp-9 and ybtS genes, which are required for yersiniabactin biosynthesis, are part of mobile pathogenicity islands (42). Other ICS genes might also be part of pathogenicity islands and, as such, are transmissible between different bacteria.…”

Section: Discussionmentioning

confidence: 91%

Isochorismate Synthase (PchA), the First and Rate-limiting Enzyme in Salicylate Biosynthesis of Pseudomonas aeruginosa

Gaille

Reimmann

Haas

2003

Journal of Biological Chemistry

103

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In Pseudomonas aeruginosa the extracellular metabolite and siderophore pyochelin is synthesized from two major precursors, chorismate and L-cysteine via salicylate as an intermediate. The regulatory role of isochorismate synthase, the first enzyme in the pyochelin biosynthetic pathway, was studied. This enzyme is encoded by pchA, the last gene in the pchDCBA operon. The PchA protein was purified to apparent electrophoretic homogeneity from a PchA-overexpressing P. aeruginosa strain. The native enzyme was a 52-kDa monomer in solution, and its activity strictly depended on Mg 2؉ . At pH 7.0, the optimum, a K m ‫؍‬ 4.5 M and a k cat ‫؍‬ 43.1 min ؊1 were determined for chorismate. No feedback inhibitors or other allosteric effectors were found. The intracellular PchA concentration critically determined the rate of salicylate formation both in vitro and in vivo. In cultures grown in iron-limiting media to high cell densities, overexpression of the pchA gene resulted in overproduction of salicylate as well as in enhanced pyochelin formation. From this work and earlier studies, it is proposed that one important factor influencing the flux through the pyochelin biosynthetic pathway is the PchA concentration, which is determined at a transcriptional level, with pyochelin acting as a positive signal and iron as a negative signal.

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Section: Discussionmentioning

confidence: 91%

Isochorismate Synthase (PchA), the First and Rate-limiting Enzyme in Salicylate Biosynthesis of Pseudomonas aeruginosa

Gaille

Reimmann

Haas

2003

Journal of Biological Chemistry

103

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“…YbtP and YbtQ from the high-pathogenicity island of Y. pestis represent domain fusion proteins comprising a TMS domain and an NBF, and hence, the composition of YbtPQ resembles an ABC-type secretion system. Together with the Fe-yersiniabactin OM receptor FyuA, YbtPQ was sufficient to restore Fe-yersiniabactin-supported growth in the enterobactin-deficient strain E. coli H1884 but not in the nonpathogenic strain Y. enterocolitica NF-O, suggesting that there are additional factors needed (e.g., a periplasmic binding protein), which are not provided in every case (33). Thus, the necessity for a periplasmic binding protein for YbtPQ-mediated Fe-yersiniabactin uptake is still in question.…”

Section: General Steps Of Siderophore Pathwaysmentioning

confidence: 99%

Siderophore-Based Iron Acquisition and Pathogen Control

Miethke

Marahiel

2007

Microbiol Mol Biol Rev

1,440

1,302

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SUMMARY High-affinity iron acquisition is mediated by siderophore-dependent pathways in the majority of pathogenic and nonpathogenic bacteria and fungi. Considerable progress has been made in characterizing and understanding mechanisms of siderophore synthesis, secretion, iron scavenging, and siderophore-delivered iron uptake and its release. The regulation of siderophore pathways reveals multilayer networks at the transcriptional and posttranscriptional levels. Due to the key role of many siderophores during virulence, coevolution led to sophisticated strategies of siderophore neutralization by mammals and (re)utilization by bacterial pathogens. Surprisingly, hosts also developed essential siderophore-based iron delivery and cell conversion pathways, which are of interest for diagnostic and therapeutic studies. In the last decades, natural and synthetic compounds have gained attention as potential therapeutics for iron-dependent treatment of infections and further diseases. Promising results for pathogen inhibition were obtained with various siderophore-antibiotic conjugates acting as “Trojan horse” toxins and siderophore pathway inhibitors. In this article, general aspects of siderophore-mediated iron acquisition, recent findings regarding iron-related pathogen-host interactions, and current strategies for iron-dependent pathogen control will be reviewed. Further concepts including the inhibition of novel siderophore pathway targets are discussed.

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“…In addition the siderophore yersiniabactin, which acts as a virulence factor for pathogenic yersinia strains growing in mice, is part of another iron transport system (83). Expression of pathogenicity by Yersinia requires the presence of a 70-kb pYV virulence plasmid that is found in high-and low-level-pathogenic strains (11,83). Differences in mouse virulence seem to be chromosomally determined.…”

Section: Yersiniabactin Introductionmentioning

confidence: 99%

Genetics and Assembly Line Enzymology of Siderophore Biosynthesis in Bacteria

Crosa

Walsh

2002

Microbiol Mol Biol Rev

726

697

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The regulatory logic of siderophore biosynthetic genes in bacteria involves the universal repressor Fur, which acts together with iron as a negative regulator. However in other bacteria, in addition to the Fur-mediated mechanism of regulation, there is a concurrent positive regulation of iron transport and siderophore biosynthetic genes that occurs under conditions of iron deprivation. Despite these regulatory differences the mechanisms of siderophore biosynthesis follow the same fundamental enzymatic logic, which involves a series of elongating acyl-S-enzyme intermediates on multimodular protein assembly lines: nonribosomal peptide synthetases (NRPS). A substantial variety of siderophore structures are produced from similar NRPS assembly lines, and variation can come in the choice of the phenolic acid selected as the N-cap, the tailoring of amino acid residues during chain elongation, the mode of chain termination, and the nature of the capturing nucleophile of the siderophore acyl chain being released. Of course the specific parts that get assembled in a given bacterium may reflect a combination of the inventory of biosynthetic and tailoring gene clusters available. This modular assembly logic can account for all known siderophores. The ability to mix and match domains within modules and to swap modules themselves is likely to be an ongoing process in combinatorial biosynthesis. NRPS evolution will try out new combinations of chain initiation, elongation and tailoring, and termination steps, possibly by genetic exchange with other microorganisms and/or within the same bacterium, to create new variants of iron-chelating siderophores that can fit a particular niche for the producer bacterium

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Functional analysis of yersiniabactin transport genes of Yersinia enterocolitica

Cited by 53 publications

References 50 publications

Isochorismate Synthase (PchA), the First and Rate-limiting Enzyme in Salicylate Biosynthesis of Pseudomonas aeruginosa

Isochorismate Synthase (PchA), the First and Rate-limiting Enzyme in Salicylate Biosynthesis of Pseudomonas aeruginosa

Siderophore-Based Iron Acquisition and Pathogen Control

Genetics and Assembly Line Enzymology of Siderophore Biosynthesis in Bacteria

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