Instruct: Identify the main category of Biorxiv papers based on the titles and abstracts
Query: Antifungal siderophore conjugates for theranostic applications in invasive pulmonary aspergillosis using low molecular TAFC scaffolds Invasive pulmonary aspergillosis (IPA) is a life-threatening form of fungal infection, primarily in immunocompromised patients and associated with a significant mortality. Diagnostic procedures are often invasive and/or time consuming and existing antifungals can be constrained by dose limiting toxicity and drug interaction. In this study, we modified triacetylfusarinine C (TAFC), the main siderophore produced by the opportunistic pathogen Aspergillus fumigatus, with antifungal molecules to perform antifungal susceptibility tests and molecular imaging.

MethodsA variation of small organic molecules (eflornithine, fludioxonil, thiomersal, fluoroorotic acid (FOA), cyanine 5 (Cy5)) with antifungal activity were coupled to TAFC, resulting in a "Trojan horse" to deliver antifungal compounds specifically into Aspergillus fumigatus hyphae by the major facilitator transporter MirB. Radioactive labelling with gallium-68 allowed to perform in vitro characterization (LogD, stability, uptake assay) as well as biodistribution experiments and PET/CT imaging in an IPA rat infection model. Compounds labelled with stable gallium were used for antifungal susceptibility tests.

Results[Ga]DAFC-fludioxonil, -FOA and Cy5 revealed a MirB dependent active uptake with fungal growth inhibition at 16 g/mL after 24 h. Visualization of an Aspergillus fumigatus infection in lungs of a rat was possible with gallium-68 labelled compounds using PET/CT. Heterogeneous biodistribution patterns revealed the immense influence of the antifungal moiety conjugated to DAFC.

ConclusionOverall, novel antifungal siderophore conjugates with promising fungal growth inhibition and the possibility to perform PET-imaging, combine both therapeutic and diagnostic potential in a theranostic compound for IPA caused by Aspergillus fumigatus.
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The categories of this paper are: education
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The categories of this paper are: cognition
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The categories of this paper are: immunology
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The categories of this paper are: evolutionary
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The categories of this paper are: molecular
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The categories of this paper are: bioinformatics
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The categories of this paper are: biochemistry
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The categories of this paper are: ecology
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The categories of this paper are: synthetic
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The categories of this paper are: developmental
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The categories of this paper are: toxicology
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The categories of this paper are: cell
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The categories of this paper are: neuroscience
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The categories of this paper are: communication
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The categories of this paper are: genetics
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The categories of this paper are: physiology