A5011444223- Antifungal resistance and susceptibility
- Fungal Infections and Studies
- Peptidase Inhibition and Analysis
- Fungal and yeast genetics research
- Helminth infection and control
- Mycotoxins in Agriculture and Food
- Polysaccharides and Plant Cell Walls
- Fungal Biology and Applications
- Cellular transport and secretion
- Nail Diseases and Treatments
- Bacterial Identification and Susceptibility Testing
- Radiomics and Machine Learning in Medical Imaging
- Essential Oils and Antimicrobial Activity
- Probiotics and Fermented Foods
- Pneumonia and Respiratory Infections
- Synthesis and Biological Evaluation
- Antimicrobial agents and applications
- Studies on Chitinases and Chitosanases
- Infectious Diseases and Mycology
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Parasitic Diseases Research and Treatment
- Medical Imaging Techniques and Applications
- Silymarin and Mushroom Poisoning
- Neuropeptides and Animal Physiology
- Ubiquitin and proteasome pathways
Leibniz-Institut für Naturstoff-Forschung und Infektionsbiologie e. V. - Hans-Knöll-Institut (HKI)
2020-2023
Innsbruck Medical University
2016-2022
Universität Innsbruck
2018-2022
Early diagnosis of invasive aspergillosis (IA) remains challenging, with available diagnostics being limited by inadequate sensitivities and specificities. Triacetylfusarinine C, a fungal siderophore that has been shown to accumulate in urine animal models, is potential new biomarker for IA.
Both branched-chain amino acids (BCAA) and iron are essential nutrients for eukaryotic cells. Previously, the Zn2Cys6-type transcription factor Leu3/LeuB was shown to play a crucial role in regulation of BCAA biosynthesis nitrogen metabolism Saccharomyces cerevisiae Aspergillus nidulans. In this study, we found that A. fumigatus homolog LeuB is involved not only but also acquisition including siderophore metabolism. Lack caused growth defect, which cured by supplementation with leucine or...
Aspergillus fumigatus (A. fumigatus) is a human pathogen causing severe invasive fungal infections, lacking sensitive and selective diagnostic tools. A. secretes the siderophore desferri-triacetylfusarinine C (TAFC) to acquire iron from host. TAFC can be labelled with gallium-68 perform positron emission tomography (PET/CT) scans. Here, we aimed chemically modify fluorescent dyes combine PET/CT optical imaging for hybrid applications. Starting ferric diacetylfusarinine ([Fe]DAFC), different...
Siderophore-mediated acquisition of iron has been shown to be indispensable for the virulence several fungal pathogens, siderophore transporter Sit1 was found mediate uptake novel antifungal drug VL-2397, and siderophores were useful as biomarkers well imaging infections. However, in filamentous fungi is poorly characterized. The opportunistic human pathogen Aspergillus fumigatus possesses five putative transporters. Here, we demonstrate that transporters Sit2 have overlapping, unique,...
Aspergillus fumigatus is responsible for thousands of cases invasive fungal disease annually. For iron uptake, A. secretes so-called siderophores, which are taken up after the binding environmental iron.
In contrast to mammalia, fungi are able synthesize the branched-chain amino acid leucine de novo. Recently, transcription factor LeuB has been shown cross-regulate biosynthesis, nitrogen metabolism and iron homeostasis in Aspergillus fumigatus, most common human mold pathogen. Moreover, biosynthetic pathway intermediate α-isopropylmalate (α-IPM) previously posttranslationally activate homologs S. cerevisiae A. nidulans. Here, we demonstrate that fumigatus inactivation of both enzymes α-IPM...
Aspergillus fumigatus produces the siderophore triacetylfusarinine C (TAFC) for iron acquisition which is essential its virulence. Therefore, TAFC a specific marker invasive aspergillosis. We have shown previously that positron emission tomography (PET) imaging with [68Ga]TAFC exhibited excellent targeting properties in an A. rat infection model. In this study, we aimed to prepare analogs modifying fusarinine (FSC) by acylation different carbon chain lengths as well charged substituents and...
Current suboptimal treatment options of invasive fungal infections and emerging resistance the corresponding pathogens urge need for alternative therapy strategies require identification novel antifungal targets. Aspergillus fumigatus, is most common airborne opportunistic mold pathogen causing often fatal disease. Establishing a in vivo conditional gene expression system, we demonstrate that downregulation class 1 lysine deacetylase (KDAC) RpdA leads to avirulence A. fumigatus murine model...
Cholecystokinin-2 receptors (CCK2R) are overexpressed in a variety of malignant diseases and therefore have gained certain attention for peptide receptor radionuclide imaging. Among extensive approaches to improve pharmacokinetics metabolic stability minigastrin (MG) based radioligands, the concept multivalency enhanced tumour targeting has not been investigated extensively. We utilized fusarinine C (FSC) as chelating scaffold novel mono-, di-, trimeric bioconjugates CCK2R expression....
Stomatin is an integral membrane protein that contributes to the uptake of microbes, e.g., spores human-pathogenic fungus Aspergillus fumigatus . By generation a stomatin-deficient macrophage line by advanced genetic engineering, we found stomatin involved in recruitment β-glucan receptor dectin-1 phagosomal macrophages.
We describe the synthesis of hydrophilic poly(poly(ethylene glycol) methyl ether methacrylate) (PmPEGMA) and hydrophobic poly(methyl (PMMA) caspofungin conjugates by a post-polymerization modification copolymers containing 10 mol % pentafluorophenyl methacrylate (PFPMA), which were obtained via reversible addition–fragmentation chain transfer copolymerization. The coupling clinically used antifungal was confirmed quantified in detail combination 1H-, 19F- diffusion-ordered NMR spectroscopy,...
Triacetylfusarinine C (TAFC) is a siderophore produced by certain fungal species and might serve as highly useful biomarker for the fast diagnosis of invasive aspergillosis. Due to its renal elimination, found in urine samples patients suffering from Aspergillus infections. Accordingly, non-invasive this easily obtainable body fluid possible. Within our contribution, we demonstrate how Raman microspectroscopy enables sensitive specific detection TAFC. We characterized TAFC iron complex...
Conidia of the airborne human-pathogenic fungus Aspergillus fumigatus are inhaled by humans. In lung, they phagocytosed alveolar macrophages and intracellularly processed. macrophages, however, conidia can interfere with maturation phagolysosomes to avoid their elimination. To investigate whether polymeric particles (PPs) reach this intracellular pathogen in we formulated dye-labeled PPs a size allowing for phagocytosis. were efficiently taken up RAW 264.7 found phagolysosomes. When infected...
Abstract Alveolar macrophages are among the first cells to come into contact with inhaled fungal conidia of human pathogenic fungus Aspergillus fumigatus . In lung alveoli, they contribute phagocytosis and elimination conidia. As a counter defense, contain grey-green pigment allowing them survive in phagosomes for some time. Previously, we showed that this conidial interferes formation flotillin-dependent lipid-rafts phagosomal membrane thereby preventing functional phagolysosomes. study,...