Identification of Ni-(l-His)2 as a substrate for NikABCDE-dependent nickel uptake in Escherichia coli

Chivers, Péter T.; Benanti, Erin; Heil-Chapdelaine, V.; Iwig, Jeffrey S.; Rowe, Jessica L.

doi:10.1039/c2mt20139a

Cited by 60 publications

(47 citation statements)

References 48 publications

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“…Moreover, this trace nickel is thought to be predominantly bound by host-derived ligands (15,16). Indeed, the NikA substrate is not free nickel Ni(II) but rather a Ni-(L-histidine)2 complex (17). The ability of Ybt, another nitrogen heterocycle, to form nickel complexes raises the question of whether Ybt facilitates nutritional nickel uptake in uropathogenic E. coli.…”

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confidence: 99%

Uropathogenic enterobacteria use the yersiniabactin metallophore system to acquire nickel

Robinson¹,

Lowe²,

Koh³

et al. 2018

Journal of Biological Chemistry

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Invasive gram-negative bacteria often express multiple virulence-associated metal ion chelators to combat host-mediated metal deficiencies. Escherichia coli, Klebsiella, and Yersinia pestis isolates encoding the Yersinia High Pathogenicity Island (HPI) secrete yersiniabactin (Ybt), a metallophore originally shown to chelate iron ions during infection. However, our recent demonstration that Ybt also scavenges copper ions during infection led us to question whether it might be capable of retrieving other metals as well. Here, we find that uropathogenic E. coli also use Ybt to bind extracellular nickel ions. Using quantitative mass spectrometry, we show that the canonical metal-Ybt import pathway internalizes the resulting Ni-Ybt complexes, extracts the nickel, and releases metal-free Ybt back to the extracellular space. We find that E. coli and Klebsiella direct the nickel liberated from this pathway to intracellular nickel enzymes. Thus, Ybt may provide access to nickel that is inaccessible to the conserved NikABCDE permease system. Nickel should be considered alongside iron and copper as a plausible substrate for Ybt-mediated metal import by enterobacteria during human infections.E. coli and related enterobacteria are the predominant cause of human urinary tract infections (UTIs) and contribute substantially to the worldwide rise in antibiotic-resistant infections (1). Clinical enterobacterial isolates often possess additional, non-essential, virulenceassociated genes. Prominent among these is the Yersinia high pathogenicity island (HPI), which encodes the biosynthetic machinery to make the specialized metabolites yersiniabactin (Ybt) and escherichelin (2). Direct mass spectrometric detection of urinary Ybt in UTI patients, serological markers, transcriptional signatures, and experimental infection models all indicate active expression of Yersinia HPI proteins during UTI pathogenesis (3-7).Although initially understood as a siderophore-a chelator that binds Fe(III) for bacterial use-Ybt has recently been appreciated to exhibit a broader metal ion binding repertoire. Copper-Ybt complexes were observed in E. coli UTI patients and were connected to protection of E. coli from copper toxicity (7), an example of biological metal passivation. Because copper is an important nutrient, complete sequestration of copper ions by Ybt could starve uropathogenic E. coli (UPEC) of copper. However, UPEC retain nutritional access to Ybt-bound copper and iron by importing the metal-Ybt complexes in a controlled manner, extracting the metal, and using it to support metal-dependent cellular functions (8). These findings implicate Ybt as an agent of nutritional passivation, a biological strategy in which metal ion toxicity is minimized Ybt-mediated nickel acquisition 2 while nutritional access is preserved. In this manner, Ybt acts as an extracellular metal ion sink, with subsequent entry into the cell occurring as a controlled process. Whether this nutritional passivation activity of Ybt extends to biological metal ions beyon...

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confidence: 99%

Uropathogenic enterobacteria use the yersiniabactin metallophore system to acquire nickel

Robinson¹,

Lowe²,

Koh³

et al. 2018

Journal of Biological Chemistry

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“…A recent study has shown that NikA binds a (L-His) 2 Ni complex, and that Ni(II) and L-His are likely co-transported through the E. coli NikABCDE system. 18 The presence of a similar complex has been demonstrated for the periplasmic binding protein CeuE in H. pylori. 19 It has been hypothesized that the presence of nickel complexes could occur in other systems.…”

Section: Introductionmentioning

confidence: 63%

“…Efficiency of the NikABCDE-dependent Ni transport in E. coli cells increases when Ni is complexed with (L-His) 2 . 18 Consistently, the crystal structure of the periplasmic nickel-binding protein NikA of E. coli in complex with Ni-(L-His) 2 has been subsequently described. 35 More recently, a similar crystal structure of the analogous CeuE periplasmic component that is supposed to be involved in nickel/cobalt acquisition together with the ABCtransporter components FecD/FecE in H. pylori has also been reported.…”

Section: Kinetics Of Nickel Transportmentioning

confidence: 89%

Rhizobium leguminosarum HupE is a highly-specific diffusion facilitator for nickel uptake

et al. 2015

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Bacteria require nickel transporters for the synthesis of Ni-containing metalloenzymes in natural, low nickel habitats. In this work we carry out functional and topological characterization of Rhizobium leguminosarum HupE, a nickel permease required for the provision of this element for [NiFe] hydrogenase synthesis. Expression studies in the Escherichia coli nikABCDE mutant strain HYD723 revealed that HupE is a medium-affinity permease (apparent K m 227 AE 21 nM; V max 49 AE 21 pmol Ni 2+ min À1 mg À1 bacterial dry weight) that functions as an energy-independent diffusion facilitator for the uptake of Ni(II) ions. This Ni 2+ transport is not inhibited by similar cations such as Mn 2+ , Zn 2+ , or Co 2+ , but is blocked by Cu 2+ . Analysis of site-directed HupE mutants allowed the identification of several residues (H36, D42, H43, F69, E90, H130, and E133) that are essential for HupE-mediated Ni uptake in E. coli cells. By using translational fusions to reporter genes we demonstrated the presence of five transmembrane domains with a periplasmic N-terminal domain and a C-terminal domain buried in the lipid bilayer. The periplasmic N-terminal domain contributes to stability and functionality of the protein.

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“…Experiments using wild-type and mutant E. coli strains showed that exogenous L-histidine was the best candidate for the nickel-complexing ligand. 17 No other molecule used, including polycarboxylic acids, provided even a modest fraction of the Ni(II)-uptake rate observed with L-His. The concentration dependence of Ni-uptake as well as binding to purified NikA both supported a ternary complex with a stoichiometry of Ni:2L-His:NikA.…”

Section: Abc-type Transportersmentioning

confidence: 99%

“…17,19 This transporter, initially annotated as Opp5A, has been shown to be important in S. aureus-linked urinary tract infections. 29 The…”

Section: S Aureus Nikamentioning

confidence: 99%

Nickel recognition by bacterial importer proteins

Chivers

2015

Metallomics

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The full-text may be used and/or reproduced, and given to third parties in any format or medium, without prior permission or charge, for personal research or study, educational, or not-for-prot purposes provided that:• a full bibliographic reference is made to the original source • a link is made to the metadata record in DRO • the full-text is not changed in any way The full-text must not be sold in any format or medium without the formal permission of the copyright holders.Please consult the full DRO policy for further details. This review compares the structural basis of nickel-recognition in the complexes (ABC and ECF-type) that dominate primary (ATP-dependent) transport, with a focus on how the structures suggest mechanisms for Ni selectivity. The structures raise key questions about the mechanisms of nickeltransfer reactions involved in import. There is also a discussion of key experimental approaches necessary to help establish the physiological importance of these structures.

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Identification of Ni-(l-His)2 as a substrate for NikABCDE-dependent nickel uptake in Escherichia coli

Cited by 60 publications

References 48 publications

Uropathogenic enterobacteria use the yersiniabactin metallophore system to acquire nickel

Uropathogenic enterobacteria use the yersiniabactin metallophore system to acquire nickel

Rhizobium leguminosarum HupE is a highly-specific diffusion facilitator for nickel uptake

Nickel recognition by bacterial importer proteins

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