@article{SpringerWaltherRickertsetal.2019,
  author    = {Springer, Jan and Walther, Grit and Rickerts, Volker and Hamprecht, Axel and Willinger, Birgit and Teschner, Daniel and Einsele, Hermann and Kurzai, Oliver and Loeffler, Juergen},
  title     = {Detection of Fusarium Species in Clinical Specimens by Probe-Based Real-Time PCR},
  series = {Journal of Fungi},
  volume    = {5},
  journal   = {Journal of Fungi},
  number    = {4},
  issn      = {2309-608X},
  doi       = {10.3390/jof5040105},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-193111},
  pages     = {105},
  year      = {2019},
  abstract  = {The mold Fusarium is a ubiquitous fungus causing plant, animal and human infections. In humans, Fusarium spp. are the major cause of eye infections in patients wearing contact lenses or after local trauma. Systemic infections by Fusarium spp. mainly occur in immunosuppressed patients and can disseminate throughout the human body. Due to high levels of resistance to antifungals a fast identification of the causative agent is an urgent need. By using a probe-based real-time PCR assay specific for the genus Fusarium we analysed several different clinical specimens detecting Fusarium spp. commonly found in clinical samples in Germany. Also, a large collection of lung fluid samples of haematological patients was analysed (n = 243). In these, two samples (0.8\%) were reproducibly positive, but only one could be confirmed by sequencing. For this case of probable invasive fungal disease (IFD) culture was positive for Fusarium species. Here we describe a rapid, probe-based real-time PCR assay to specifically detect DNA from a broad range of Fusarium species and its application to clinically relevant specimens.},
  language  = {en}
}
@article{BelicPageLazariotouetal.2019,
  author    = {Belic, Stanislav and Page, Lukas and Lazariotou, Maria and Waaga-Gasser, Ana Maria and Dragan, Mariola and Springer, Jan and Loeffler, Juergen and Morton, Charles Oliver and Einsele, Hermann and Ullmann, Andrew J. and Wurster, Sebastian},
  title     = {Comparative Analysis of Inflammatory Cytokine Release and Alveolar Epithelial Barrier Invasion in a Transwell® Bilayer Model of Mucormycosis},
  series = {Frontiers in Microbiology},
  volume    = {9},
  journal   = {Frontiers in Microbiology},
  doi       = {10.3389/fmicb.2018.03204},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-252477},
  year      = {2019},
  abstract  = {Understanding the mechanisms of early invasion and epithelial defense in opportunistic mold infections is crucial for the evaluation of diagnostic biomarkers and novel treatment strategies. Recent studies revealed unique characteristics of the immunopathology of mucormycoses. We therefore adapted an alveolar Transwell® A549/HPAEC bilayer model for the assessment of epithelial barrier integrity and cytokine response to Rhizopus arrhizus, Rhizomucor pusillus, and Cunninghamella bertholletiae. Hyphal penetration of the alveolar barrier was validated by 18S ribosomal DNA detection in the endothelial compartment. Addition of dendritic cells (moDCs) to the alveolar compartment led to reduced fungal invasion and strongly enhanced pro-inflammatory cytokine response, whereas epithelial CCL2 and CCL5 release was reduced. Despite their phenotypic heterogeneity, the studied Mucorales species elicited the release of similar cytokine patterns by epithelial and dendritic cells. There were significantly elevated lactate dehydrogenase concentrations in the alveolar compartment and epithelial barrier permeability for dextran blue of different molecular weights in Mucorales-infected samples compared to Aspergillus fumigatus infection. Addition of monocyte-derived dendritic cells further aggravated LDH release and epithelial barrier permeability, highlighting the influence of the inflammatory response in mucormycosis-associated tissue damage. An important focus of this study was the evaluation of the reproducibility of readout parameters in independent experimental runs. Our results revealed consistently low coefficients of variation for cytokine concentrations and transcriptional levels of cytokine genes and cell integrity markers. As additional means of model validation, we confirmed that our bilayer model captures key principles of Mucorales biology such as accelerated growth in a hyperglycemic or ketoacidotic environment or reduced epithelial barrier invasion upon epithelial growth factor receptor blockade by gefitinib. Our findings indicate that the Transwell® bilayer model provides a reliable and reproducible tool for assessing host response in mucormycosis.},
  language  = {en}
}