Detection of a Serum Siderophore by LC-MS/MS as a Potential Biomarker of Invasive Aspergillosis

Carroll, Cassandra; Amankwa, Lawrence N.; Pinto, Linda J.; Fuller, Jeffrey; Moore, Margo M.

doi:10.1371/journal.pone.0151260

Cited by 36 publications

(47 citation statements)

References 53 publications

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“…15]. 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].…”

Section: Microbial Siderophoresmentioning

confidence: 99%

Siderophores for molecular imaging applications

Petřík

Zhai

Haas

et al. 2016

Clin Transl Imaging

110

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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: Microbial Siderophoresmentioning

confidence: 99%

Siderophores for molecular imaging applications

Petřík

Zhai

Haas

et al. 2016

Clin Transl Imaging

110

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“…In general, current strategies to target pathogen iron acquisition include the use of iron chelation therapy, siderophore-drug conjugates, inhibitors of uptake systems or biosynthetic enzymes, vaccines against surface uptake components, and immunological strategies to influence iron availability to intra and extracellular pathogens. 93–99 The approach of targeting biosynthetic enzymes for inhibitor development shows considerable promise for pathogens that deploy siderophores during host colonization. 97 Success in this area was recently demonstrated in a screen using an assay for the L-ornithine- N 5 -monooxygenase encoded by sidA in A. fumigatus .…”

Section: Targeting Iron Acquisition To Augment Antifungal Therapymentioning

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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“…Triacetylfusarinine C (TAFC) is another secondary metabolite that has been used as a biomarker of Aspergillus infection. It is a siderophore that scavenges iron for fungal growth during infection . TAFC is relatively unique to Aspergillus and has, therefore, been proposed as a method to predict aspergillosis .…”

Section: Metabolicmentioning

confidence: 99%

“…It is a siderophore that scavenges iron for fungal growth during infection . TAFC is relatively unique to Aspergillus and has, therefore, been proposed as a method to predict aspergillosis . Ultra performance liquid chromatography‐tandem mass spectrometry (UPLC‐MS/MS) has quantified TAFC in human serum, and levels were found to positively correlate with GM levels (≥0.5 index threshold) .…”

Section: Metabolicmentioning

confidence: 99%

See 1 more Smart Citation

The current status of avian aspergillosis diagnoses: Veterinary practice to novel research avenues

Savelieff¹,

Pappalardo

Azmanis

2018

Veterinary Clinical Pathol

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Aspergillus fungal infections continue to be a significant cause of morbidity and mortality in birds that can, in part, be attributed to the lack of a diagnostic "gold standard" for Aspergillus infection, and which delays the diagnosis, treatment, and outcome of avian patients. At present, none of the available methods in veterinary care can detect aspergillosis early enough and with the accuracy, precision, and specificity required of an ideal diagnostic tool. Therefore, researching methods of Aspergillus detection is still an active area of inquiry, and novel techniques continue to emerge. This review will provide a brief overview of current clinical methods, with an emphasis on avian care, in addition to a series of techniques in development that could offer distinct advantages over existing methods.

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Detection of a Serum Siderophore by LC-MS/MS as a Potential Biomarker of Invasive Aspergillosis

Cited by 36 publications

References 53 publications

Siderophores for molecular imaging applications

Siderophores for molecular imaging applications

Iron acquisition in fungal pathogens of humans

The current status of avian aspergillosis diagnoses: Veterinary practice to novel research avenues

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