Siderocalins: Siderophore binding proteins evolved for primary pathogen host defense

Sia, Allyson K.; Allred, Benjamin E.; Raymond, Kenneth N.

doi:10.1016/j.cbpa.2012.11.014

Cited by 58 publications

(43 citation statements)

References 60 publications

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“…The primary function of lipocalin-2 is to sequester bacterial siderophores such as enterobactin that avidly bind ferric iron [10]. Enterobactin is secreted by certain E. coli and other enteric Gram-negative bacteria, then recaptured by the same or different bacteria that can extract its iron.…”

Section: Lipocalin-2mentioning

confidence: 99%

Iron and infection

2017

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Section: Lipocalin-2mentioning

confidence: 99%

Iron and infection

2017

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“…As a result, siderophores were suggested as biomarkers in aspergillosis and tuberculosis [16,17]. Due to the function of siderophores as virulence determinants, mammals evolved siderophore sequestering proteins, termed siderocalins, and pathogens evolved mechanisms to avoid recognition of their siderophores by siderocalins [18]. Unequivocally, siderophores play a profound role in iron acquisition of most microorganisms.…”

Section: Microbial Siderophoresmentioning

confidence: 99%

Siderophores for molecular imaging applications

Petřík

Zhai

Haas

et al. 2016

Clin Transl Imaging

107

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This review covers publications on siderophores applied for molecular imaging applications, mainly for radionuclide-based imaging. Siderophores are low molecular weight chelators produced by bacteria and fungi to scavenge essential iron. Research on these molecules has a continuing history over the past 50 years. Many biomedical applications have been developed, most prominently the use of the siderophore desferrioxamine (DFO) to tackle iron overload related diseases. Recent research described the upregulation of siderophore production and transport systems during infection. Replacing iron in siderophores by radionuclides, the most prominent Ga-68 for PET, opens approaches for targeted imaging of infection; the proof of principle has been reported for fungal infections using 68 Ga-triacetylfusarinine C (TAFC). Additionally, fluorescent siderophores and therapeutic conjugates have been described and may be translated to optical imaging and theranostic applications. Siderophores have also been applied as bifunctional chelators, initially DFO as chelator for Ga-67 and more recently for Zr-89 where it has become the standard chelator in Immuno-PET. Improved DFO constructs and bifunctional chelators based on cyclic siderophores have recently been developed for Ga-68 and Zr-89 and show promising properties for radiopharmaceutical development in PET. A huge potential from basic biomedical research on siderophores still awaits to be utilized for clinical and translational imaging.

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“…For example, mutants of P. aeruginosa with compromised pyoverdin biosynthesis exhibit attenuated pathogenesis in both C. elegans and in mice (3)(4)(5); despite this, the virulence mechanism(s) of siderophores remains unknown. Similarly, little is known about how hosts defend themselves against siderophore exposure and subsequent loss of iron; the notable exception being secretion of a siderocalin, a protein that binds siderophores and minimizes their activity (6). Given the importance of siderophores as virulence determinants, greater insight into this defense process is needed.…”

mentioning

confidence: 99%

Mitophagy confers resistance to siderophore-mediated killing by Pseudomonas aeruginosa

Kirienko

Ausubel

Ruvkun

2015

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

185

193

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In the arms race of bacterial pathogenesis, bacteria produce an array of toxins and virulence factors that disrupt core host processes. Hosts mitigate the ensuing damage by responding with immune countermeasures. The iron-binding siderophore pyoverdin is a key virulence mediator of the human pathogen Pseudomonas aeruginosa, but its pathogenic mechanism has not been established. Here we demonstrate that pyoverdin enters Caenorhabditis elegans and that it is sufficient to mediate host killing. Moreover, we show that iron chelation disrupts mitochondrial homeostasis and triggers mitophagy both in C. elegans and mammalian cells. Finally, we show that mitophagy provides protection both against the extracellular pathogen P. aeruginosa and to treatment with a xenobiotic chelator, phenanthroline, in C. elegans. Although autophagic machinery has been shown to target intracellular bacteria for degradation (a process known as xenophagy), our report establishes a role for authentic mitochondrial autophagy in the innate immune defense against P. aeruginosa.mitophagy | Pseudomonas | siderophore | innate immunity | C. elegans

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Siderocalins: Siderophore binding proteins evolved for primary pathogen host defense

Cited by 58 publications

References 60 publications

Iron and infection

Iron and infection

Siderophores for molecular imaging applications

Mitophagy confers resistance to siderophore-mediated killing by Pseudomonas aeruginosa

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