Harnessing the power of fungal siderophores for the imaging and treatment of human diseases

Szebesczyk, Agnieszka; Olshvang, Evgenia; Shanzer, Abraham; Carver, Peggy L.; Gumienna‐Kontecka, Elżbieta

doi:10.1016/j.ccr.2016.05.001

Cited by 34 publications

(29 citation statements)

References 240 publications

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“…Table 1 summarizes applications of siderophores as imaging agents. They can be prepared either by the introduction of appropriate radiometal to the natural (iron-)siderophore complex via the exchange of iron or artificially by the modification of natural siderophore with a chromophore suitable for optical imaging [31][32][33][34]. Already in the 1970s and 1980s, first investigations of radiolabelled siderophores, including desferrioxamine (DFO), were already reported with gamma-emitting radionuclides- 67 Ga and 111 In [35][36][37][38].…”

Section: Siderophores For Molecular Imaging Of Infectionmentioning

confidence: 99%

“…infections showed promising results; nevertheless, it warrants further investigation. Moreover, a number of studies on complex siderophore-drug conjugates have been made to test their potential as effective antimicrobial agents [23,34,[61][62][63]. It could be speculated that these siderophore conjugates could be radiolabelled or derivatized and used for molecular imaging of infections.…”

Section: Siderophores For Molecular Imaging Of Infectionmentioning

confidence: 99%

“…The recognition of the role of siderophores as important microbial iron transporters has led to the exploitation of this pathway in a 'Trojan Horse' strategy not only for pathogen detection, but also for the development of therapeutic strategies [34,59]. Banin et al [60] have used siderophore-metal complex combining a strong siderophore, DFO with non-radioactive gallium for the treatment of Pseudomonas aeruginosa (P.a.)…”

Section: Siderophores For Molecular Imaging Of Infectionmentioning

confidence: 99%

“…The microbial activity was not altered by the attachment of various functionalities and fluorescent siderophore analogues became invaluable tools in the investigation of molecular mechanisms involved in microbial iron transport and acquisition. Accordingly, these artificial siderophore analogues could also serve as a tool for in vivo diagnostic imaging or targeting of microbial pathogens [34].…”

Section: Siderophores For Molecular Imaging Of Infectionmentioning

confidence: 99%

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Siderophores for molecular imaging applications

Petřík

Zhai

Haas

et al. 2016

Clin Transl Imaging

106

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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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Section: Siderophores For Molecular Imaging Of Infectionmentioning

confidence: 99%

Section: Siderophores For Molecular Imaging Of Infectionmentioning

confidence: 99%

Section: Siderophores For Molecular Imaging Of Infectionmentioning

confidence: 99%

Section: Siderophores For Molecular Imaging Of Infectionmentioning

confidence: 99%

See 2 more Smart Citations

Siderophores for molecular imaging applications

Petřík

Zhai

Haas

et al. 2016

Clin Transl Imaging

106

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“…We refer readers to several recent reviews for additional considerations of iron homeostasis in fungi, including mechanisms of regulation and opportunities for therapy. 10–16 …”

Section: Introductionmentioning

confidence: 99%

Iron acquisition in fungal pathogens of humans

2017

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The devastating infections that fungal pathogens cause in humans are underappreciated relative to viral, bacterial and parasitic diseases. In recent years, the contributions to virulence of reductive iron uptake, siderophore-mediated uptake and heme acquisition have been identified in the best studied and most life-threatening fungal pathogens: Candida albicans, Cryptococcus neoformans and Aspergillus fumigatus. In particular, exciting new work illustrates the importance of iron acquisition from heme and hemoglobin in the virulence of pathogenic yeasts. However, the challenge of establishing how these fungi gain access to hemoglobin in blood and to other sources of heme remains to be fully addressed. Recent studies are also expanding our knowledge of iron uptake in less-well studied fungal pathogens, including dimorphic fungi where new information reveals an integration of iron acquisition with morphogenesis and cell-surface properties for adhesion to host cells. Overall, the accumulating information provides opportunities to exploit iron acquisition for antifungal therapy, and new work highlights the development of specific inhibitors of siderophore biosynthesis and metal chelators for therapeutic use alone or in conjunction with existing antifungal drugs. It is clear that iron-related therapies will need to be customized for specific diseases because the emerging view is that fungal pathogens use different combinations of strategies for iron acquisition in the varied niches of vertebrate hosts.

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Multivalente Siderophor‐DOTAM‐Konjugate als Theranostika zur Visualisierung und Behandlung bakterieller Infektionen

Ferreira

Fetz

et al. 2017

Angewandte Chemie

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Es besteht ein großer Bedarf an besseren Diagnosen von Infektionen in tieferliegenden Kçrperregionen durch nichtinvasive molekulare Bildgebung. In diesem Zusammenhang wurden Sonden entwickelt, die auf Siderophor-Konjugaten mit Catechol-Einheiten und einem zentralenD OTAM-Kern beruhen. Diese Sonden kçnnen sowohlein Metallion als auche inen antibiotischen Wirkstoff tragen und eignen sich daher fürtheranostische Anwendungen. Die Translokation der Konjugate durchd ie innere und äußere Zellmembran von E. coli wurde durch Experimente zur Wiederherstellung des Wachstums mit Enterobactin-defizienten Bakterienstämmen, durch die antibakterielle WirkungA mpicillin-tragender Konjugate sowie durch Konfokalmikroskopie bestätigt. FürL etztere wurde ein auf E. coli adaptiertes System aus Fluorogenaktivierendem Protein und Malachitgrünverwendet. Eine erste Anwendung der Verbindungen fürd ie In-vivo-Bildgebung wurde mit einem Cy5.5-Konjugat in P. -aeruginosa-infizierten Mäusen gezeigt.

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Harnessing the power of fungal siderophores for the imaging and treatment of human diseases

Cited by 34 publications

References 240 publications

Siderophores for molecular imaging applications

Siderophores for molecular imaging applications

Iron acquisition in fungal pathogens of humans

Multivalente Siderophor‐DOTAM‐Konjugate als Theranostika zur Visualisierung und Behandlung bakterieller Infektionen

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