Petrobactin, a Photoreactive Siderophore Produced by the Oil-Degrading Marine Bacterium <i>Marinobacter hydrocarbonoclasticus</i>

Barbeau, Katherine A.; Zhang, Guangping; Live, David; Butler, Alison

doi:10.1021/ja0119088

Cited by 186 publications

(123 citation statements)

References 7 publications

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“…This result implies that production of PB is necessary for the full pathogenicity of B. anthracis. PB, first isolated from the marine bacterium Marinobacter hydrocarbonoclasticus (12), is an unusual hexadentate citrate-and 3,4-dihydroxybenzoate-containing natural siderophore (13). To our knowledge, a complete hexadentate 3,4-catecholate siderophore has never been observed in a pathogenic bacterium other than B. anthracis and the related Bacillus cereus.…”

mentioning

confidence: 99%

Anthrax pathogen evades the mammalian immune system through stealth siderophore production

Abergel

Wilson

Arceneaux

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

181

213

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Systemic anthrax, caused by inhalation or ingestion of Bacillus anthracis spores, is characterized by rapid microbial growth stages that require iron. Tightly bound and highly regulated in a mammalian host, iron is scarce during an infection. To scavenge iron from its environment, B. anthracis synthesizes by independent pathways two small molecules, the siderophores bacillibactin (BB) and petrobactin (PB). Despite the great efficiency of BB at chelating iron, PB may be the only siderophore necessary to ensure full virulence of the pathogen. In the present work, we show that BB is specifically bound by siderocalin, a recently discovered innate immune protein that is part of an antibacterial iron-depletion defense. In contrast, neither PB nor its ferric complex is bound by siderocalin. Although BB incorporates the common 2,3-dihydroxybenzoyl iron-chelating subunit, PB is novel in that it incorporates the very unusual 3,4-dihydroxybenzoyl chelating subunit. This structural variation results in a large change in the shape of both the iron complex and the free siderophore that precludes siderocalin binding, a stealthy evasion of the immune system. Our results indicate that the blockade of bacterial siderophore-mediated iron acquisition by siderocalin is not restricted to enteric pathogenic organisms and may be a general defense mechanism against several different bacterial species. Significantly, to evade this innate immune response, B. anthracis produces PB, which plays a key role in virulence of the organism. This analysis argues for antianthrax strategies targeting siderophore synthesis and uptake.bacillibactin ͉ Bacillus anthracis ͉ petrobactin ͉ siderocalin

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mentioning

confidence: 99%

Anthrax pathogen evades the mammalian immune system through stealth siderophore production

Abergel

Wilson

Arceneaux

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

181

213

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“…6 Photolysis of the complex into the citrate ligand-to-metal charge-transfer band is reported to result in decarboxylation and oxidation of the ligand, forming a 3-ketoglutarate residue at the former site of the citryl moiety ( Figure S1). 6 This process also involves reduction of the metal center; 10 in fact when 0.1 mM solutions of [Fe III (PB)] 3-and [Ga III (PB)] 3-contained in quartz cuvettes are exposed to sunlight, no spectral change is observed for [Ga III (PB)] 3-whereas the photolysis of [Fe III (PB)] 3-is characterized by significant changes ( Figure S2). 11 The incorporation of 3,4-catecholate and citrate units in PB therefore presents a challenge for a full description of the thermodynamic properties of the ligand.…”

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confidence: 99%

Petrobactin-Mediated Iron Transport in Pathogenic Bacteria: Coordination Chemistry of an Unusual 3,4-Catecholate/Citrate Siderophore

2008

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Because bacterial growth and infection rely on adequate iron supply, the ability to scavenge iron in the iron-limited environment of the host is a virulence trait for pathogenic microorganisms. 2 To mediate their mandatory iron acquisition, the zoonotic causative agent of anthrax, Bacillus anthracis, and the human opportunistic pathogen Bacillus cereus both synthesize, by independent pathways, two low-molecular-weight ferric ion chelators, the hexadentate siderophores bacillibactin (BB) and petrobactin (PB) (Figure 1). 3 While BB is built on a central trilactone scaffold, linked to the common 2,3-dihydroxybenzoyl iron-chelating subunits, and exhibits a phenomenally high and selective affinity for iron (K f ) 10 48 ), 4 it is specifically bound by the mammalian protein siderocalin, a component of the antibacterial iron-depletion defense of the innate immune system. 5 Conversely, PB, first isolated from the marine bacterium Marinobacter hydrocarbonoclasticus, 6 is an unusual citrate-and 3,4-catecholate-based ligand, 7 the only natural hexadentate 3,4-catecholate siderophore observed in a pathogenic bacterium. Moreover, the full pathogenicity of B. anthracis in mice is observed only when PB is produced. 8 The protein siderocalin cannot accommodate 3,4-catecholate moieties within its binding pocket, precluding sequestration of PB. Hence, incorporation of such iron-binding moieties into a siderophore has been proposed as a bacterial strategy to evade the immune system. 5 However, little is known about the iron coordination chemistry of 3,4-catecholamide fragments. 9 Are the thermodynamic and kinetic properties of the ferric PB complex advantageous as compared to other more common hydroxamate and citrate siderophores?Another notable feature of PB is the photoreactivity of its ferric complex. 6 Photolysis of the complex into the citrate ligand-to-metal charge-transfer band is reported to result in decarboxylation and oxidation of the ligand, forming a 3-ketoglutarate residue at the former site of the citryl moiety ( Figure S1). 6 This process also involves reduction of the metal center; 10 in fact when 0.1 mM solutions of [Fe III (PB)] 3-and [Ga III (PB)] 3-contained in quartz cuvettes are exposed to sunlight, no spectral change is observed for [Ga III (PB)] 3-whereas the photolysis of [Fe III (PB)] 3-is characterized by significant changes ( Figure S2). 11 The incorporation of 3,4-catecholate and citrate units in PB therefore presents a challenge for a full description of the thermodynamic properties of the ligand. Indeed, while the 3,4-dihydroxybenzamide units are susceptible to oxidation and decomposition at high pH, compromising accurate pK a determination by potentiometric methods, 12 the photoreactivity of the ferric-citrate moiety requires rigorous dark conditions for spectrophotometric competition titrations. However, the affinities of PB and its photoproduct (PB ν ) for Fe(III) at physiological pH were measured via competition titration against EDTA. Titrations were performed on PB samples stored in the dark ov...

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“…The ferric complex of petrobactin undergoes a ligand-to-metal charge-transfer reaction resulting in decarboxylation and oxidation of the citryl moiety forming 3-ketoglutarate. 48 Rhizobium meliloti, capable of fixing atmospheric nitrogen when symbiotically associated with certain legumes, excretes and utilizes rhizobactin DM4 (Figure 3(a)), N 2 -[2-{(1-carboxymethyl)amino}ethyl]-N 6 -(3-carboxy-3-hydroxy-1-oxopropyl)lysine. Iron binding is achieved via ethylenediaminedicarboxyland α-hydroxycarboxyl-ligands.…”

Section: Carboxylate-type Siderophoresmentioning

confidence: 99%

Iron Transport: Siderophores

Matzanke¹

2005

Encyclopedia of Inorganic and Bioinorganic Chemistry

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Siderophores (from the Greek: iron carrier) are low molecular mass (500–1500 Da) iron chelators that are synthesized in bacteria and fungi under conditions of iron deficiency. Siderophores exhibit extraordinarily high complex formation constants for ferric iron with β‐values ranging from 10 20 to approximately 10 50 . Fe 2+ ‐siderophores are some 20 orders of magnitude less stable than their Fe 3+ counterparts. The d5 electronic configuration of Fe 3+ rules out any crystal field stabilization energy and makes ferric iron complexes relatively labile with respect to isomerization and ligand exchange. Siderophores display a selectivity for iron that is reflected in the corresponding complex stability constants that are higher with Fe 3+ than with Al 3+ , or with bivalent cations like Ca 2+ , Cu 2+ or Zn 2+ . Microorganisms excrete desferrisiderophores in order to scavenge iron from the environment. The competition for iron by siderophores, the mechanisms of siderophore uptake through microbial membranes, and the intracellular pathways of siderophore‐iron utilization strongly depend on thermodynamic, kinetic, and structural features of the ferric iron siderophore complexes. The structural features of siderophores are diverse. The ligating groups contain oxygen atoms of hydroxamate, catecholate, α‐hydroxy carboxylic and salicylic acids, or oxazoline and thiazoline nitrogen. Reduction potentials of ferric siderophore complexes vary between −700 and −150 mV. In particular at the low potential end below −450 mV, special biological strategies of reductive iron removal are required because these potentials are too negative for typical cellular reductases. The coordination and redox chemistry of siderophores is also reflected in the mechanisms of siderophore‐mediated iron uptake in microorganisms. A classic example is the intracellular removal of iron from enterobactin. The permeation of cell walls or bacterial membranes by siderophores is in most microbes a highly specific process requiring an array of up to eight proteins. The advent of modern molecular biology delivered a cornucopia of methods enabling high‐yield production of specific gene products relevant to siderophore synthesis and transport, analyses of structure‐function relationships (employing site directed mutagenesis), and detailed insights into the regulation of the corresponding processes. One siderophore, ferrioxamine B, serves as a detoxifier in iron overload diseases and in the treatment of β‐thalassemia. Siderophores and siderophore analogs also play a role in MRI and are employed as basic models for actinide chelators in order to remove these metals from the environment or from a contaminated body.

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Petrobactin, a Photoreactive Siderophore Produced by the Oil-Degrading Marine Bacterium Marinobacter hydrocarbonoclasticus

Cited by 186 publications

References 7 publications

Anthrax pathogen evades the mammalian immune system through stealth siderophore production

Anthrax pathogen evades the mammalian immune system through stealth siderophore production

Petrobactin-Mediated Iron Transport in Pathogenic Bacteria: Coordination Chemistry of an Unusual 3,4-Catecholate/Citrate Siderophore

Iron Transport: Siderophores

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