Pyoverdine

Last updated
Pyoverdine
Pyoverdine.svg
Names
Other names
Pyoverdin
Identifiers
3D model (JSmol)
ChEBI
PubChem CID
  • InChI=1S/C56H88N18O22/c1-27(79)43-53(91)61-15-4-3-8-31(46(84)65-34(11-7-19-73(96)26-78)49(87)70-44(28(2)80)54(92)71-43)64-47(85)33(10-6-18-72(95)25-77)67-50(88)36(23-75)68-48(86)32(9-5-16-62-56(58)59)66-51(89)37(24-76)69-52(90)38-14-17-60-45-35(63-42(83)13-12-30(57)55(93)94)20-29-21-40(81)41(82)22-39(29)74(38)45/h20-22,25-28,30-34,36-38,43-45,60,75-76,79-82,95-96H,3-19,23-24,57H2,1-2H3,(H,61,91)(H,63,83)(H,64,85)(H,65,84)(H,66,89)(H,67,88)(H,68,86)(H,69,90)(H,70,87)(H,71,92)(H,93,94)(H4,58,59,62)
  • Key: QIRRYPHVUMPBDX-UARRTFJPSA-N
  • CC(C1C(=O)NC(C(=O)NCCCCC(C(=O)NC(C(=O)N1)CCCN(C=O)O)NC(=O)C(CCCN(C=O)O)NC(=O)C(CO)NC(=O)C(CCCN=C(N)N)NC(=O)C(CO)NC(=O)C2CCNC3N2C4=CC(=C(C=C4C=C3NC(=O)CCC(C(=O)O)N)O)O)C(C)O)O
Properties
C56H88N18O22
Molar mass 1365.424 g·mol−1
AppearanceSolid
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
Yes check.svgY  verify  (what is  Yes check.svgYX mark.svgN ?)

Pyoverdines [1] (alternatively, and less commonly, spelled as pyoverdins) are fluorescent siderophores produced by certain pseudomonads. [2] [3] Pyoverdines are important virulence factors, and are required for pathogenesis in many biological models of infection. Their contributions to bacterial pathogenesis include providing a crucial nutrient (i.e., iron), regulation of other virulence factors (including exotoxin A and the protease PrpL), [4] supporting the formation of biofilms, [5] and are increasingly recognized for having toxicity themselves. [6] [7] [8]

Contents

Pyoverdines have also been investigated as "Trojan Horse" molecules for the delivery of antimicrobials to otherwise resistant bacterial strains, as chelators that can be used for bioremediation of heavy metals, and as fluorescent reporters used to assay for the presence of iron and potentially other metals. [9]

Due to their bridging the gaps between pathogenicity, iron metabolism, and fluorescence, pyoverdines have piqued the curiosity of scientists around the world for over 100 years.[ citation needed ]

Biological functions

Like most siderophores, pyoverdine is synthesized and secreted into the environment when the microorganism that produces it detects that intracellular iron concentrations have fallen below a preset threshold. Although iron is the fourth-most abundant element in the Earth's crust, solubility of biologically relevant iron compounds is exceedingly low, and is generally insufficient for the needs of most (but not all) microorganisms. Siderophores, which are typically quite soluble and have exceptionally high avidity for iron (III) (the avidity of some siderophores for iron exceeds 1040 M-1 and many of the strongest avidities ever observed in nature are exhibited by siderophores for iron), help increase bioavailability of iron by pulling it into aqueous solution.

In addition to this role, pyoverdine has a number of other functions, including regulating virulence, [4] [5] limiting the growth of other bacterial species (and serving as a sort of antimicrobial) by limiting iron availability, and sequestering other metals and preventing their toxicity.

Structure and characteristics

Although many (>100) forms of pyoverdine have been isolated and studied, they all have certain characteristics in common. Each pyoverdine molecule has three parts: a dihydroxyquinoline core, a 6-14 amino acid peptide that varies among strains, and a side chain (usually composed of a 4-5 carbon α-ketoacid from the Krebs/citric acid cycle). The core of pyoverdine is responsible for several of its properties, including its well-known yellowish color and fluorescence.

Structure

The dihydroxyquinoline core is composed of (1S)-5-amino-2,3-dihydro- 8,9-dihydroxy-1H-pyrimido[1,2-a]quinoline-1-carboxylic acid. This portion of the molecule is invariant amongst all observed pyoverdine molecules.

The core is modified by the addition of an amino acid chain composed of 6-14 amino acids. The chain of amino acids is built onto the chromophore core, and is synthesized via non-ribosomal peptide synthesis. [10] [11] As is common for non-ribsosomally synthesized peptides, pyoverdine frequently includes D-form amino acids and non-standard amino acids, such as N-5-formyl-N-5-hydroxyornithine. The peptide chain may also be partially (or completely) cyclized. This peptide chain provides the other four aspects of the hexadentate interaction, usually through hydroxamate and/or hydroxycarboxylate groups. This portion of the molecule is also crucial for interaction with the ferripyoverdine receptor (FpvA) that allows ferripyoverdine to be imported into the cell. The peptide chain produced by a given strain of Pseudomonas is currently thought to be invariant.

Little is known about the particular function or importance of the ketoacid side chain, but it is well known [12] that pyoverdine molecules with different ketoacids (congeners) co-exist. Ketoacids that have been observed include succinate/succinamide, glutamate, glutarate, malate/malamide, and α-ketoglutarate.

Structure of the peptide backbone in various fluorescent Pseudomonas strains. Amino acid three-letter codes are used, along with Q=chromophore, DXxx=D-amino acid, aThr=allo-threonine, c=cyclic structure, cOHOrn=cyclo-hydroxyornithine, Dab=diaminobutyric acid, Ac=Acetyl, Fo=formyl OH=hydroxyl [13]
Pseudomonad speciesStrainStructure of the pyoverdine peptide chain
P. aeruginosaATCC15692 (PAO1)Q-DSer-Arg-DSer-FoOHOrn-c(Lys-FoOHOrn-Thr-Thr)
P. aeruginosaATCC27853Q-DSer-FoOHDOrn-Orn-Gly-aDThr-Ser-cOHOrn
P. aeruginosaPa6Q-DSer-Dab-FoOHOrn-Gln-DGln-FoOHDOrn-Gly
P. chlororaphisATCC9446Q-DSer-Lys-Gly-FoOHOrn-c(Lys-FoOHDOrn-Ser)
P. fluorescens bv.IATCC13525Q-DSer-Lys-Gly-FoOHOrn-c(Lys-FoOHDOrn-Ser)
P. fluorescens bv.I9AWQ-DSer-Lys-OHHis-aDThr-Ser-cOHOrn
P. fluorescens bv.IIIATCC17400Q-DAla-DLys-Gly-Gly-OHAsp-DGln/Dab-Ser-DAla-cOHOrn
P. fluorescens bv.V51WQ-DAla-DLys-Gly-Gly-OHDAsp-DGln-DSer-Ala-Gly-aDThr-cOHOrn
P. fluorescens bv.V1WQ-DSer-Lys-Gly-FoOHOrn-c(Lys-FoOHDOrn-Ser)
P. fluorescens bv.V10CWQ-DSer-Lys-Gly-FoOHOrn-c(Lys-FoOHDOrn-Ser)
P. fluorescens bv.VIPL7Q-DSer-AcOHDOrn-Ala-Gly-aDThr-Ala-cOHOrn
P. fluorescens bv.VIPL8Q-DLys-AcOHDOrn-Ala-Gly-aDThr-Ser-cOHOrn
P. fluorescens1.3Q-DAla-DLys-Gly-Gly-OHAsp-DGln/Dab-Gly-Ser-cOHOrn
P. fluorescens18.1Q-DSer-Lys-Gly-FoOHOrn-Ser-DSer-Gly-c(Lys-FoOHDOrn-Ser)
P. fluorescensCCM 2798Q-Ser-Dab-Gly-Ser-OHDAsp-Ala-Gly-DAla-Gly-cOHOrn
P. fluorescensCFBP 2392Q-DLys-AcOHDOrn-Gly-aDThr-Thr-Gln-Gly-DSer-cOHOrn
P. fluorescensCHA0Q-Asp-FoOHDOrn-Lys-c(Thr-Ala-Ala-FoOHDOrn-Lys)
P. putida bv. B9BWQ-DSer-Lys-OHHis-aDThr-Ser-cOHOrn
P. putidaCFBP 2461Q-Asp-Lys-OHDAsp-Ser-aDThr-Ala-Thr-DLys-cOHOrn
P. tolaasiiNCPPB 2192Q-DSer-Lys-Ser-DSer-Thr-Ser-AcOHOrn-Thr-DSer-cOHDOrn

Characteristics

Amongst their other notable characteristics, pyoverdines exhibit bright, relatively photostable fluorescence with characteristic excitation and emission spectra that are rapidly and strongly quenched upon binding their natural ligand, iron. Excitation and molar absorptivity show moderate pH dependence, but fluorescence is generally unaffected by pH variations. Unlike fluorescence, spectroscopic absorption shows little quenching upon iron-binding, suggesting that the mechanism for molecular relaxation is vibrational, rather than via electromagnetic radiation.

Pyoverdine coordinates a hexadentate (i.e., six-part) chelation of iron that involves six different oxygen atoms (2 from the dihyodroxyquinoline core and 2 from each of 2 different amino acids in the backbone). This results in a very tightly coordinated octahedral complex that efficiently prevents the ingress of water or other materials that may disrupt binding. Typically, ferric iron is removed from pyoverdine by reduction to the ferrous state, for which pyoverdine has a much lower (i.e., 109 M-1) avidity. This allows for the non-destructive removal of iron from pyoverdine. After reduction, the iron is "handed off" to other carriers that have increased affinity for ferrous iron, while the apopyoverdine is re-exported for continued use.

Pyoverdine is structurally similar to azobactin, from Azotobacter vinelandii , except that the latter possesses an extra urea ring. [13]

Synthesis

Biosynthesis

In Pseudomonas aeruginosa PAO1 there are 14 pvd genes involved in the biosynthesis of pyoverdine. [14]

Pyoverdine biosynthesis seems to be largely regulated through the activity of the alternate sigma factor PvdS which, in turn, is regulated both by the Fur system and by the intracellular sequestration of PvdS at the plasma membrane and away from the nucleoid by the repressor FpvI.

Despite significant investigation, relatively little is known about the biosynthesis of pyoverdine. For example, It remains unclear whether the biosynthesis of pyoverdine takes place as individual components (i.e., the core, the peptide chain, and the ketoacid) or if the core and the other parts are condensed as a beginning molecule (possibly by the PvdL protein) and then modified by other enzymes afterward. For reasons that remain unclear, pyoverdine biosynthesis is strongly inhibited by the anti-cancer therapeutic fluorouracil, [15] particularly through its ability to disrupt RNA metabolism. [16] Although production of pyoverdines varies from strain to strain, fluorescent Pseudomonas species have been shown to produce between 200 and 500 mg/L when grown in iron-depleted conditions. [17] [18]

Core

There is some dispute about the origin of the fluorescent chromophore core. Originally, it was widely thought to be synthesized by the pvcABCD operon, as deletion of portions of the pvcC and pvcD genes disrupts pyoverdine production. [19] Like other aspects of pyoverdine biosynthesis, the regulation of the pvcABCD is iron-dependent, and the loss of these genes' activity resulted in pyoverdine disruption.

A separate report suggests that pvcABCD may be responsible for the synthesis of paerucumarin (a pseudoverdine-related molecule) instead, and claims that loss of activity in the locus has no effect on pyoverdine production. [20] In addition, some fluorescent Pseudomonads lack apparent homologs of these genes, further calling into question whether this is the function of these genes.

This is consistent with reports that pvdL combines coenzyme A to a myristic acid moiety, then adds a glutamate, D-tyrosine, and L-2,4-diaminobutyric acid (DAB). [21] An alternate biosynthetic pathway suggests that pvdL incorporates glutamate, 2,4,5-trihydroxyphenylalanine and L-2,4-daminobutyric acid instead. [22] This latter is supported by the identification of incorporation of a radiolabeled tyrosine into either pyoverdine or pseudoverdine.

This discrepancy remains unresolved.

Peptide chain

Several of the genes responsible for pyoverdine biosynthesis (e.g., pvdH, pvdA, and pvdF) are involved in the generation of precursor and alternate amino acids necessary for various portions of the molecule. [23] Several others (e.g., pvdI, and pvdJ) are directly responsible for "stitching" together the peptide chain. [23] pvdD terminates the chain and releases the precursor into the cytoplasm, which is consistent with identification of pyoverdine-like molecules in the cytoplasm with incompletely matured chromophores. [23]

Ketoacid

Currently, the best available evidence suggests that the ketoacid is originally attached to the chromophore core (as L-glutamate) when it is synthesized from D-tyrosine, L-2,4-diaminobutyric acid, and L-glutamate. It is unclear how this is later altered to the other congenerate (i.e., a-ketoglutarate, succinate/succinamide, etc.) forms.

Maturation and export

The localization of some of the Pvd proteins in the periplasm and the outer membrane (such as PvdN, PvdO, PvdP, and PvdQ) have been interpreted to suggest that portions of the maturation of pyoverdine takes place in this location, perhaps after being transported into the periplasm by PvdE, which is homologous to ABC type exporters. How completely matured pyoverdine is exported from the cell remains unclear. Once completely matured, pyoverdine is exported from the periplasm by PvdRT-OpmQ efflux pump.

Total chemical synthesis

A complete organic synthesis pathway for the pyoverdine produced by P. aeruginosa strain PAO1 has been reported [24] using solid-phase peptide synthesis. This protocol yielded pyoverdine at high yield (~48%) and is expected to substantially increase the ability of scientists to generate targeted derivatives on the pyoverdine scaffold and to facilitate the creation of siderophores with antimicrobial warheads.

Mechanisms of virulence

Pyoverdine has been reported to be required for virulence in a variety of disease models, including C. elegans and various models of murine infection (e.g., burn models, pneumonia models, etc.). [6] [15] [25]

As noted above, pyoverdine contributes in several fashions to general virulence, including regulating the production of itself, exotoxin A (which stalls translation), and the protease PrpL. [4] There is also evidence that, although not essential for its formation, pyoverdine contributes to the production and development of biofilms that are important for virulence. [5]

Finally, pyoverdine is associated with several types of toxicity in its own right. In 2001, Albesa and colleagues reported that pyoverdine purified from a strain of P. fluorescens exhibited profound cytotoxicity to mammalian macrophages and that this effect was at least partially dependent upon reactive oxygen species. [26] Later, Kirienko and colleagues determined that pyoverdine is both necessary and sufficient for killing C. elegans, that enters host cells, destabilizes mitochondrial dynamics, and induces a hypoxic response. [6] [7] Exposure triggers a response that is consistent with hypoxia that depends on the HIF-1 protein, suggesting that the host perceives a condition where it lacks the molecular tools for generating ATP (generally, iron, oxygen, and cellular reducing equivalents). [6] [7]

Role in microbial cooperation

Once pyoverdine is secreted, it diffuses freely in the environment. Iron-bound pyoverdine (also known as ferripyoverdine) can be taken up by any bacterial cell with the appropriate receptor, although this varies between strains. [27] Importantly, this creates a common good which can be exploited by 'cheaters' which retain the ability to use pyoverdine but have stopped making it. Since pyoverdine production is energetically costly, this can create a fitness advantage in cells that are not synthesizing it. [28] [29] [30] [31] Consequently, pyoverdine has become a model trait to study microbial cooperation and exploitation. [32] [33]

In P. aeruginosa , pyoverdine non-producing “cheat” bacteria have been shown to i) evolve readily from a producing ancestor; [34] and ii) outcompete cooperating strains in mixed culture in a density- and frequency-dependent manner. [35] [36] Since pyoverdine usage relies on passive diffusion and pyoverdine production is metabolically costly, environmental conditions are known to influence the likelihood of successful exploitation. The competitive advantage of pyoverdine non-producers over producers in mixed culture was shown to be maximized when environments are well-mixed and molecules diffuse readily (low spatial structure) and when the costs and benefits of pyoverdine production are high, i.e. when iron is strongly limited. [30] [37] Most studies on pyoverdine cooperation and cheating have been conducted using clinical isolates, but siderophore exploitation was recently also demonstrated in natural Pseudomonas isolates from non-clinical samples. [38] [39]

Nomenclature

Currently, no widespread and systematic nomenclature is used to differentiate pyoverdine structures. A system was proposed in 1989, [40] consisting of Pyoverdine Type I, Type IIa, Type IIb, and Type III. At the time, only a few pyoverdine structures were known, and it was anticipated that much less variation would occur than has been seen. As a consequence of the tremendous heterogeneity observed in the peptide backbone, and the observation of congeners (pyoverdines from a single strain differing only in their ketoacid portions), nomenclature of pyoverdines remains rather tenuous and no single system has garnered universal acceptance.

History

Other uses

Pseudoverdine

A compound related to pyoverdine, called pseudoverdine (formally known as 3-formylamino-6,7-dihydroxycoumarin) is also produced by some fluorescent Pseudomonads. [41] It is thought that pseudoverdine and pyoverdine may arise from a common precursor, 2,4,5-trihydroxyphenylalanine, which may condense with L-2,4-diaminobutyric acid to initiate pyoverdine production. [41]

Pseudoverdine is relatively similar to pyoverdine in its fluorescence and other spectroscopic properties, and its ability to chelate ferric iron, albeit at much lower affinity. [41] Unlike pyoverdine, it is incapable of transporting iron into cells, likely due to the absence of the peptide chain. [41] Another dissimilarity is that pseudoverdine does not appear to be regulated by the same processes as pyoverdine. [41]

Related Research Articles

<span class="mw-page-title-main">Peptide bond</span> Covalent chemical bond between amino acids in a peptide or protein chain

In organic chemistry, a peptide bond is an amide type of covalent chemical bond linking two consecutive alpha-amino acids from C1 of one alpha-amino acid and N2 of another, along a peptide or protein chain.

<i>Pseudomonas</i> Genus of Gram-negative bacteria

Pseudomonas is a genus of Gram-negative bacteria belonging to the family Pseudomonadaceae in the class Gammaproteobacteria. The 313 members of the genus demonstrate a great deal of metabolic diversity and consequently are able to colonize a wide range of niches. Their ease of culture in vitro and availability of an increasing number of Pseudomonas strain genome sequences has made the genus an excellent focus for scientific research; the best studied species include P. aeruginosa in its role as an opportunistic human pathogen, the plant pathogen P. syringae, the soil bacterium P. putida, and the plant growth-promoting P. fluorescens, P. lini, P. migulae, and P. graminis.

<i>Pseudomonas fluorescens</i> Species of bacterium

Pseudomonas fluorescens is a common Gram-negative, rod-shaped bacterium. It belongs to the Pseudomonas genus; 16S rRNA analysis as well as phylogenomic analysis has placed P. fluorescens in the P. fluorescens group within the genus, to which it lends its name.

<span class="mw-page-title-main">Polymyxin</span> Group of antibiotics

Polymyxins are antibiotics. Polymyxins B and E are used in the treatment of Gram-negative bacterial infections. They work mostly by breaking up the bacterial cell membrane. They are part of a broader class of molecules called nonribosomal peptides.

<span class="mw-page-title-main">Siderophore</span> Iron compounds secreted by microorganisms

Siderophores (Greek: "iron carrier") are small, high-affinity iron-chelating compounds that are secreted by microorganisms such as bacteria and fungi. They help the organism accumulate iron. Although a widening range of siderophore functions is now being appreciated, siderophores are among the strongest (highest affinity) Fe3+ binding agents known. Phytosiderophores are siderophores produced by plants.

Nonribosomal peptides (NRP) are a class of peptide secondary metabolites, usually produced by microorganisms like bacteria and fungi. Nonribosomal peptides are also found in higher organisms, such as nudibranchs, but are thought to be made by bacteria inside these organisms. While there exist a wide range of peptides that are not synthesized by ribosomes, the term nonribosomal peptide typically refers to a very specific set of these as discussed in this article.

<span class="mw-page-title-main">Pseudomonadaceae</span> Family of gram-negative bacteria

The Pseudomonadaceae are a family of bacteria which includes the genera Azomonas, Azorhizophilus, Azotobacter, Mesophilobacter, Pseudomonas, and Rugamonas. The family Azotobacteraceae was recently reclassified into this family.

<i>Aspergillus fumigatus</i> Species of fungus

Aspergillus fumigatus is a species of fungus in the genus Aspergillus, and is one of the most common Aspergillus species to cause disease in individuals with an immunodeficiency.

<i>Pseudomonas aeruginosa</i> Species of bacterium

Pseudomonas aeruginosa is a common encapsulated, Gram-negative, aerobic–facultatively anaerobic, rod-shaped bacterium that can cause disease in plants and animals, including humans. A species of considerable medical importance, P. aeruginosa is a multidrug resistant pathogen recognized for its ubiquity, its intrinsically advanced antibiotic resistance mechanisms, and its association with serious illnesses – hospital-acquired infections such as ventilator-associated pneumonia and various sepsis syndromes.

Adhesins are cell-surface components or appendages of bacteria that facilitate adhesion or adherence to other cells or to surfaces, usually in the host they are infecting or living in. Adhesins are a type of virulence factor.

<span class="mw-page-title-main">Phenazine</span> Chemical compound

Phenazine is an organic compound with the formula (C6H4)2N2. It is a dibenzo annulated pyrazine, and the parent substance of many dyestuffs, such as the toluylene red, indulines, and safranines (and the closely related eurhodines). Phenazine crystallizes in yellow needles, which are only sparingly soluble in alcohol. Sulfuric acid dissolves it, forming a deep-red solution.

Autoinducers are signaling molecules that are produced in response to changes in cell-population density. As the density of quorum sensing bacterial cells increases so does the concentration of the autoinducer. Detection of signal molecules by bacteria acts as stimulation which leads to altered gene expression once the minimal threshold is reached. Quorum sensing is a phenomenon that allows both Gram-negative and Gram-positive bacteria to sense one another and to regulate a wide variety of physiological activities. Such activities include symbiosis, virulence, motility, antibiotic production, and biofilm formation. Autoinducers come in a number of different forms depending on the species, but the effect that they have is similar in many cases. Autoinducers allow bacteria to communicate both within and between different species. This communication alters gene expression and allows bacteria to mount coordinated responses to their environments, in a manner that is comparable to behavior and signaling in higher organisms. Not surprisingly, it has been suggested that quorum sensing may have been an important evolutionary milestone that ultimately gave rise to multicellular life forms.

<span class="mw-page-title-main">Pyocyanin</span> Chemical compound

Pyocyanin (PCN−) is one of the many toxic compounds produced and secreted by the Gram negative bacterium Pseudomonas aeruginosa. Pyocyanin is a blue secondary metabolite, turning red below pH 4.9, with the ability to oxidise and reduce other molecules and therefore kill microbes competing against P. aeruginosa as well as mammalian cells of the lungs which P. aeruginosa has infected during cystic fibrosis. Since pyocyanin is a zwitterion at blood pH, it is easily able to cross the cell membrane. There are three different states in which pyocyanin can exist: oxidized (blue), monovalently reduced (colourless) or divalently reduced (red). Mitochondria play an important role in the cycling of pyocyanin between its redox states. Due to its redox-active properties, pyocyanin generates reactive oxygen species.

<span class="mw-page-title-main">Yersiniabactin</span> Chemical compound

Yersiniabactin (Ybt) is a siderophore found in the pathogenic bacteria Yersinia pestis, Yersinia pseudotuberculosis, and Yersinia enterocolitica, as well as several strains of enterobacteria including enteropathogenic Escherichia coli and Salmonella enterica. Siderophores, compounds of low molecular mass with high affinities for ferric iron, are important virulence factors in pathogenic bacteria. Iron—an essential element for life used for such cellular processes as respiration and DNA replication—is extensively chelated by host proteins like lactoferrin and ferritin; thus, the pathogen produces molecules with an even higher affinity for Fe3+ than these proteins in order to acquire sufficient iron for growth. As a part of such an iron-uptake system, yersiniabactin plays an important role in pathogenicity of Y. pestis, Y. pseudotuberculosis, and Y. entercolitica.

<span class="mw-page-title-main">Rhamnolipid</span> Chemical compound

Rhamnolipids are a class of glycolipid produced by Pseudomonas aeruginosa, amongst other organisms, frequently cited as bacterial surfactants. They have a glycosyl head group, in this case a rhamnose moiety, and a 3-(hydroxyalkanoyloxy)alkanoic acid (HAA) fatty acid tail, such as 3-hydroxydecanoic acid.

<span class="mw-page-title-main">L-ornithine N5 monooxygenase</span> Enzyme

L-ornithine N5 monooxygenase (EC 1.14.13.195 or EC 1.14.13.196) is an enzyme which catalyzes one of the following chemical reactions:

L-ornithine + NADPH + O2 N(5)-hydroxy-L-ornithine + NADP+ + H2O L-ornithine + NAD(P)H + O2 N(5)-hydroxy-L-ornithine + NAD(P)+ + H2O

Ornibactin is a siderophore, or small iron-binding compound secreted by bacteria to transport iron into the cell. Ornibactin is produced by Burkholderia cenocepacia under iron-deficient conditions. B. cenocepacia is known to opportunistically infect humans, specifically ones suffering from cystic fibrosis.

<small>D</small>-Amino acid Class of chemical compounds

ᴅ-Amino acids are amino acids where the stereogenic carbon alpha to the amino group has the ᴅ-configuration. For most naturally-occurring amino acids, this carbon has the ʟ-configuration. ᴅ-Amino acids are occasionally found in nature as residues in proteins. They are formed from ribosomally-derived ᴅ-amino acid residues.

<span class="mw-page-title-main">Elisa Granato</span> Microbiologist

Elisa Teresa Granato is a molecular microbiologist in the Departments of Zoology and Biochemistry at the University of Oxford, where she researches bacterial interactions and how they evolved, including the significance of features of bacteria that contribute to disease, also known as virulence factors.

<span class="mw-page-title-main">Pyonitrin</span> Chemical compound

Pyonitrins are a family of highly hydrogen-deficient alkaloids discovered from an insect-associated Pseudomonas protegens strain. In vivo, pyonitrins A-D show activity against pathogen Candida albicans, which commonly cause bloodstream infections.

References

  1. ↑ For the purposes of this page, pyoverdine will generally refer (unless otherwise noted) to the pyoverdine produced by Pseudomonas aeruginosa strain PAO1. It has been subjected to the most extensive study and can be considered the prototypical siderophore.
  2. ↑ S. Wendenbaum; P. Demange; A. Dell; J. M. Meyer; M. A. Abdallah (1983). "The structure of pyoverdine Pa, the siderophore of Pseudomonas aeruginosa". Tetrahedron Letters. 24 (44): 4877–4880. doi:10.1016/S0040-4039(00)94031-0.
  3. ↑ Menhart, N.; Thariath, A.; Viswanatha, T. (1991). "Characterization of the pyoverdines of Azotobacter vinelandii ATCC 12837 with regard to heterogeneity". Biology of Metals. 4 (4): 223–32. doi:10.1007/bf01141185. PMID   1838001. S2CID   8712926.
  4. 1 2 3 Lamont, Iain L.; Beare, Paul A.; Ochsner, Urs; Vasil, Adriana I.; Vasil, Michael L. (2002-05-14). "Siderophore-mediated signaling regulates virulence factor production in Pseudomonasaeruginosa". Proceedings of the National Academy of Sciences of the United States of America. 99 (10): 7072–7077. Bibcode:2002PNAS...99.7072L. doi: 10.1073/pnas.092016999 . ISSN   0027-8424. PMC   124530 . PMID   11997446.
  5. 1 2 3 Banin, Ehud; Vasil, Michael L.; Greenberg, E. Peter (2005-08-02). "Iron and Pseudomonas aeruginosa biofilm formation". Proceedings of the National Academy of Sciences of the United States of America. 102 (31): 11076–11081. Bibcode:2005PNAS..10211076B. doi: 10.1073/pnas.0504266102 . ISSN   0027-8424. PMC   1182440 . PMID   16043697.
  6. 1 2 3 4 Kirienko, Natalia V.; Kirienko, Daniel R.; Larkins-Ford, Jonah; Wählby, Carolina; Ruvkun, Gary; Ausubel, Frederick M. (2013-04-17). "Pseudomonas aeruginosa disrupts Caenorhabditis elegans iron homeostasis, causing a hypoxic response and death". Cell Host & Microbe. 13 (4): 406–416. doi:10.1016/j.chom.2013.03.003. ISSN   1934-6069. PMC   3641844 . PMID   23601103.
  7. 1 2 3 Kirienko, Natalia V.; Ausubel, Frederick M.; Ruvkun, Gary (2015-02-10). "Mitophagy confers resistance to siderophore-mediated killing by Pseudomonas aeruginosa". Proceedings of the National Academy of Sciences of the United States of America. 112 (6): 1821–1826. Bibcode:2015PNAS..112.1821K. doi: 10.1073/pnas.1424954112 . ISSN   1091-6490. PMC   4330731 . PMID   25624506.
  8. ↑ Minandri, Fabrizia; Imperi, Francesco; Frangipani, Emanuela; Bonchi, Carlo; Visaggio, Daniela; Facchini, Marcella; Pasquali, Paolo; Bragonzi, Alessandra; Visca, Paolo (2016-08-01). "Role of Iron Uptake Systems in Pseudomonas aeruginosa Virulence and Airway Infection". Infection and Immunity. 84 (8): 2324–2335. doi:10.1128/IAI.00098-16. ISSN   1098-5522. PMC   4962624 . PMID   27271740.
  9. ↑ Yoder, Michael F.; Kisaalita, William S. (2011-01-01). "Iron specificity of a biosensor based on fluorescent pyoverdin immobilized in sol-gel glass". Journal of Biological Engineering. 5: 4. doi: 10.1186/1754-1611-5-4 . ISSN   1754-1611. PMC   3114707 . PMID   21554740.
  10. ↑ Hohlneicher, U.; Schäfer, M.; Fuchs, R.; Budzikiewicz, H. (2016-10-11). "Ferribactins as the biosynthetic precursors of the Pseudomonas siderophores pyoverdins". Zeitschrift für Naturforschung C. 56 (3–4): 308–310. doi: 10.1515/znc-2001-3-423 . ISSN   0939-5075. PMID   11371026.
  11. ↑ Visca, Paolo; Imperi, Francesco; Lamont, Iain L. (2007-01-01). "Pyoverdine siderophores: from biogenesis to biosignificance". Trends in Microbiology. 15 (1): 22–30. doi:10.1016/j.tim.2006.11.004. ISSN   0966-842X. PMID   17118662.
  12. ↑ Budzikiewicz, H (1997). "Siderophores of Fluorescent Pseudomonads". Zeitschrift für Naturforschung C. 52 (11–12): 713–720. doi: 10.1515/znc-1997-11-1201 . PMID   9463934. S2CID   26196277.
  13. 1 2 Meyer, J. M. (2000). "Pyoverdines: Pigments, siderophores and potential taxonomic markers of fluorescent Pseudomonas species". Archives of Microbiology. 174 (3): 135–142. doi:10.1007/s002030000188. PMID   11041343. S2CID   13283224.
  14. ↑ Lamont, I. L.; Martin, L. W. (2003). "Identification and characterization of novel pyoverdine synthesis genes in Pseudomonas aeruginosa". Microbiology. 149 (4): 833–842. doi: 10.1099/mic.0.26085-0 . PMID   12686626.
  15. 1 2 Imperi, Francesco; Massai, Francesco; Facchini, Marcella; Frangipani, Emanuela; Visaggio, Daniela; Leoni, Livia; Bragonzi, Alessandra; Visca, Paolo (2013-04-30). "Repurposing the antimycotic drug flucytosine for suppression of Pseudomonas aeruginosa pathogenicity". Proceedings of the National Academy of Sciences of the United States of America. 110 (18): 7458–7463. Bibcode:2013PNAS..110.7458I. doi: 10.1073/pnas.1222706110 . ISSN   1091-6490. PMC   3645532 . PMID   23569238.
  16. ↑ Kirienko, Daniel R.; Revtovich, Alexey V.; Kirienko, Natalia V. (2016-08-01). "A High-Content, Phenotypic Screen Identifies Fluorouridine as an Inhibitor of Pyoverdine Biosynthesis and Pseudomonas aeruginosa Virulence". mSphere. 1 (4): e00217–16. doi:10.1128/mSphere.00217-16. ISSN   2379-5042. PMC   4999921 . PMID   27579370.
  17. ↑ Cornelis, P; Hohnadel, D; Meyer, JM (1989). "Evidence for different pyoverdine-mediated iron uptake systems among Pseudomonas aeruginosa strains". Infect Immun. 57 (11): 3491–3497. doi:10.1128/IAI.57.11.3491-3497.1989. PMC   259858 . PMID   2509364.
  18. ↑ Hohnadel, Dany; Haas, Dieter; Meyer, Jean-Marie (1986-09-01). "Mapping of mutations affecting pyoverdine production in Pseudomonas aeruginosa". FEMS Microbiology Letters. 36 (2–3): 195–199. doi: 10.1111/j.1574-6968.1986.tb01695.x . ISSN   0378-1097.
  19. ↑ Stintzi, A.; Johnson, Z.; Stonehouse, M.; Ochsner, U.; Meyer, J. M.; Vasil, M. L.; Poole, K. (1999-07-01). "The pvc gene cluster of Pseudomonas aeruginosa: role in synthesis of the pyoverdine chromophore and regulation by PtxR and PvdS". Journal of Bacteriology. 181 (13): 4118–4124. doi:10.1128/JB.181.13.4118-4124.1999. ISSN   0021-9193. PMC   93907 . PMID   10383985.
  20. ↑ Clarke-Pearson, Michael F.; Brady, Sean F. (2008-10-01). "Paerucumarin, a new metabolite produced by the pvc gene cluster from Pseudomonas aeruginosa". Journal of Bacteriology. 190 (20): 6927–6930. doi:10.1128/JB.00801-08. ISSN   1098-5530. PMC   2566218 . PMID   18689486.
  21. ↑ Budzikiewicz, H (1993). "Secondary metabolites from fluorescent pseudomonads". FEMS Microbiol Rev. 10 (3–4): 209–228. doi: 10.1111/j.1574-6968.1993.tb05868.x . PMID   8318257.
  22. ↑ Stintzi, A; Cornelis, P; Hohnadel, D; Meyer, JM; Dean, C; Poole, K; Kourambas, S; Krishnapillai, V (1996). "Novel pyoverdine biosynthesis gene(s) of Pseudomonas aeruginosa PAO". Microbiology. 142 (5): 1181–1190. doi: 10.1099/13500872-142-5-1181 . PMID   8704959.
  23. 1 2 3 Cézard, C.; Farvacques, N.; Sonnet, P. (2015-01-01). "Chemistry and biology of pyoverdines, Pseudomonas primary siderophores". Current Medicinal Chemistry. 22 (2): 165–186. doi:10.2174/0929867321666141011194624. ISSN   1875-533X. PMID   25312210.
  24. ↑ Mashiach, Roi; Meijler, Michael M. (2013-04-05). "Total synthesis of pyoverdin D". Organic Letters. 15 (7): 1702–1705. doi:10.1021/ol400490s. ISSN   1523-7052. PMID   23530778.
  25. ↑ Takase, H.; Nitanai, H.; Hoshino, K.; Otani, T. (2000-04-01). "Impact of siderophore production on Pseudomonas aeruginosa infections in immunosuppressed mice". Infection and Immunity. 68 (4): 1834–1839. doi:10.1128/iai.68.4.1834-1839.2000. ISSN   0019-9567. PMC   97355 . PMID   10722571.
  26. ↑ Becerra, C.; Albesa, I.; Eraso, A. J. (2001-07-13). "Leukotoxicity of Pyoverdin, Production of Reactive Oxygen Species, and Effect of UV Radiation". Biochemical and Biophysical Research Communications. 285 (2): 414–418. doi:10.1006/bbrc.2001.5188. PMID   11444858.
  27. ↑ Bodilis, Josselin; Ghysels, Bart; Osayande, Julie; Matthijs, Sandra; Pirnay, Jean-Paul; Denayer, Sarah; De Vos, Daniel; Cornelis, Pierre (2009-08-01). "Distribution and evolution of ferripyoverdine receptors in Pseudomonas aeruginosa". Environmental Microbiology. 11 (8): 2123–2135. doi:10.1111/j.1462-2920.2009.01932.x. hdl: 2268/162362 . ISSN   1462-2920. PMID   19397675.
  28. ↑ Weigert, Michael; Kümmerli, Rolf (2017-07-12). "The physical boundaries of public goods cooperation between surface-attached bacterial cells". Proc. R. Soc. B. 284 (1858): 20170631. doi:10.1098/rspb.2017.0631. ISSN   0962-8452. PMC   5524494 . PMID   28701557.
  29. ↑ Buckling, Angus; Harrison, Freya; Vos, Michiel; Brockhurst, Michael A.; Gardner, Andy; West, Stuart A.; Griffin, Ashleigh (2007-11-01). "Siderophore-mediated cooperation and virulence in Pseudomonas aeruginosa". FEMS Microbiology Ecology. 62 (2): 135–141. doi: 10.1111/j.1574-6941.2007.00388.x . ISSN   0168-6496. PMID   17919300.
  30. 1 2 Kümmerli, Rolf; Brown, Sam P. (2010-11-02). "Molecular and regulatory properties of a public good shape the evolution of cooperation". Proceedings of the National Academy of Sciences. 107 (44): 18921–18926. Bibcode:2010PNAS..10718921K. doi: 10.1073/pnas.1011154107 . ISSN   0027-8424. PMC   2973908 . PMID   20944065.
  31. ↑ Griffin, Ashleigh S.; West, Stuart A.; Buckling, Angus (2004). "Cooperation and competition in pathogenic bacteria". Nature. 430 (7003): 1024–1027. Bibcode:2004Natur.430.1024G. doi:10.1038/nature02744. hdl: 1842/698 . ISSN   1476-4687. PMID   15329720. S2CID   4429250.
  32. ↑ West, Stuart A.; Griffin, Ashleigh S.; Gardner, Andy; Diggle, Stephen P. (2006). "Social evolution theory for microorganisms". Nature Reviews Microbiology. 4 (8): 597–607. doi:10.1038/nrmicro1461. ISSN   1740-1534. PMID   16845430. S2CID   18451640.
  33. ↑ Kümmerli, R.; Santorelli, L. A.; Granato, E. T.; Dumas, Z.; Dobay, A.; Griffin, A. S.; West, S. A. (2015-12-01). "Co-evolutionary dynamics between public good producers and cheats in the bacterium Pseudomonas aeruginosa" (PDF). Journal of Evolutionary Biology. 28 (12): 2264–2274. doi: 10.1111/jeb.12751 . ISSN   1420-9101. PMID   26348785. S2CID   826683.
  34. ↑ Dumas, Z.; Kümmerli, R. (2012-03-01). "Cost of cooperation rules selection for cheats in bacterial metapopulations". Journal of Evolutionary Biology. 25 (3): 473–484. doi: 10.1111/j.1420-9101.2011.02437.x . ISSN   1420-9101. PMID   22168669. S2CID   19132153.
  35. ↑ Ross‐Gillespie, Adin; Gardner, Andy; West, Stuart A.; Griffin, Ashleigh S. (2007-09-01). "Frequency Dependence and Cooperation: Theory and a Test with Bacteria". The American Naturalist. 170 (3): 331–342. doi:10.1086/519860. ISSN   0003-0147. PMID   17879185. S2CID   14248496.
  36. ↑ Ross-Gillespie, Adin; Gardner, Andy; Buckling, Angus; West, Stuart A.; Griffin, Ashleigh S. (2009-09-01). "Density Dependence and Cooperation: Theory and a Test with Bacteria". Evolution. 63 (9): 2315–2325. doi: 10.1111/j.1558-5646.2009.00723.x . ISSN   1558-5646. PMID   19453724. S2CID   5699402.
  37. ↑ Kümmerli, Rolf; Griffin, Ashleigh S.; West, Stuart A.; Buckling, Angus; Harrison, Freya (2009-10-07). "Viscous medium promotes cooperation in the pathogenic bacterium Pseudomonas aeruginosa". Proceedings of the Royal Society of London B: Biological Sciences. 276 (1672): 3531–3538. doi:10.1098/rspb.2009.0861. ISSN   0962-8452. PMC   2817189 . PMID   19605393.
  38. ↑ Bruce, John B.; Cooper, Guy A.; Chabas, Hélène; West, Stuart A.; Griffin, Ashleigh S. (2017-10-01). "Cheating and resistance to cheating in natural populations of the bacterium Pseudomonas fluorescens". Evolution. 71 (10): 2484–2495. doi:10.1111/evo.13328. ISSN   1558-5646. PMID   28833073. S2CID   3485902.
  39. ↑ Butaitė, Elena; Baumgartner, Michael; Wyder, Stefan; Kümmerli, Rolf (2017-09-04). "Siderophore cheating and cheating resistance shape competition for iron in soil and freshwater Pseudomonas communities". Nature Communications. 8 (1): 414. Bibcode:2017NatCo...8..414B. doi:10.1038/s41467-017-00509-4. ISSN   2041-1723. PMC   5583256 . PMID   28871205.
  40. ↑ Briskot, G.; Taraz, K.; Budzikiewicz, H. (1989). "Bacterial Constituents, XXXVII. Pyoverdin-Type Siderophores from Pseudomonas aeruginosa". Liebigs Ann Chem. 1989 (4): 375–384. doi:10.1002/jlac.198919890164.
  41. 1 2 3 4 5 Longerich, I; Taraz, K; Budzikiewicz, H; Tsai, L; Meyer, JM (1993). "Pseudoverdin, a compound related to the pyoverdin chromophore from a Pseudomonas aeruginosa strain incapable to produce pyoverdins". Z Naturforsch C. 48 (5–6): 425–429. doi: 10.1515/znc-1993-5-605 . PMID   8363709. S2CID   29269780.
This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.