Quantitative Metabolomics Reveals an Epigenetic Blueprint for Iron Acquisition in Uropathogenic Escherichia coli

Henderson, Jeffrey P.; Crowley, Jan R.; Pinkner, Jerome S.; Walker, Jennifer N.; Tsukayama, Pablo; Stamm, Walter E.; Hooton, Thomas M.; Hultgren, Scott J.

doi:10.1371/journal.ppat.1000305

Cited by 204 publications

(277 citation statements)

References 47 publications

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“…These findings corroborate a recent study (18) that showed positivity only in 14% of protein-carbohydrate interaction in this system. Though the glycosylation of proteins in bacteria is limited, other glycoconjugates are abundant (19) .…”

Section: Detection Of Iuta Gene In Upec Strainssupporting

confidence: 93%

The ferric aerobactin receptor IutA, a protein isolated on agarose column, is not essential for uropathogenic Escherichia coli infection

Landgraf

Berlese

Fernandes

et al. 2012

Rev. Latino-Am. Enfermagem

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Although many proteins have been described involved in Escherichia coli colonization and infection, only few reports have shown lectins as important components in these processes. Because the mechanisms underlying E. coli colonization process involving lectins are not fully understood, we sought to identify the presence of other non-described lectins in E. coli. Here, we isolated a 75-kDa protein from E. coli on Sepharose column and identified it as ferric aerobactin receptor (IutA). Since IutA is controversially associated with virulence of some E. coli strains, mainly in uropathogenic E. coli (UPEC), we evaluated the presence of iutA gene in UPEC isolated from patients with urinary infection. This gene was present in only 38% of the isolates, suggesting a weak association with virulence. Because there is a redundancy in the siderophore-mediated uptake systems, we suggest that IutA can be advantageous but not essential for UPEC.

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Section: Detection Of Iuta Gene In Upec Strainssupporting

confidence: 93%

The ferric aerobactin receptor IutA, a protein isolated on agarose column, is not essential for uropathogenic Escherichia coli infection

Landgraf

Berlese

Fernandes

et al. 2012

Rev. Latino-Am. Enfermagem

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“…Siderophores including yersiniabactin, salmochelin and aerobactin enable ExPEC to internalise and utilise distantly scavenged Fe 3+ for growth (35). Many ExPEC also carry genes encoding haem receptors, which enable direct haemin uptake, while others produce toxins including α-haemolysin,…”

Section: Urinary Tract Infection-associated Vfsmentioning

confidence: 99%

Extra-intestinal pathogenic Escherichia coli (ExPEC): Disease, carriage and clones

Dale

Woodford

2015

Journal of Infection

150

132

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Extra-intestinal pathogenic E. coli (ExPEC) have a complex phylogeny, broad virulence factor (VF) armament and significant genomic plasticity, and are associated with a spectrum of host infective syndromes ranging from simple urinary tract infection to life-threatening bacteraemia. Their importance as pathogens has come to the fore in recent years, particularly in the context of the global emergence of hyper-virulent and antibiotic resistant strains.Despite this, the mechanisms underlying ExPEC transmission dynamics and clonal selection remain poorly understood. Large-scale epidemiological and clinical studies are urgently required to ascertain the mechanisms underlying these processes to enable the development of novel evidence-based preventative and therapeutic strategies. In the current review, we provide a concise summary of the methods utilised for ExPEC phylogenetic genetic delineation before exploring in detail the associations between ExPEC VFs and site-specific disease. We then consider the role of ExPEC as an intestinal colonist before outlining known associations between ExPEC clonal variation, specific disease syndromes and antibiotic resistance.

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“…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)(4)(5)(6)(7).…”

mentioning

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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Quantitative Metabolomics Reveals an Epigenetic Blueprint for Iron Acquisition in Uropathogenic Escherichia coli

Cited by 204 publications

References 47 publications

The ferric aerobactin receptor IutA, a protein isolated on agarose column, is not essential for uropathogenic Escherichia coli infection

The ferric aerobactin receptor IutA, a protein isolated on agarose column, is not essential for uropathogenic Escherichia coli infection

Extra-intestinal pathogenic Escherichia coli (ExPEC): Disease, carriage and clones

Uropathogenic enterobacteria use the yersiniabactin metallophore system to acquire nickel

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