@article{LieseSchoenvanderLindenetal.2019,
  author    = {Liese, J. G. and Schoen, C. and van der Linden, M. and Lehmann, L. and Goettler, D. and Keller, S. and Maier, A. and Segerer, F. and Rose, M. A. and Streng, A.},
  title     = {Changes in the incidence and bacterial aetiology of paediatric parapneumonic pleural effusions/empyema in Germany, 2010-2017: a nationwide surveillance study},
  series = {Clinical Microbiology and Infection},
  volume    = {25},
  journal   = {Clinical Microbiology and Infection},
  doi       = {10.1016/j.cmi.2018.10.020},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-236866},
  pages     = {857-864},
  year      = {2019},
  abstract  = {Objectives Parapneumonic pleural effusions/empyema (PPE/PE) are severe complications of community-acquired pneumonia. We investigated the bacterial aetiology and incidence of paediatric PPE/PE in Germany after the introduction of universal pneumococcal conjugate vaccine (PCV) immunization for infants. Methods Children <18 years of age hospitalized with pneumonia-associated PPE/PE necessitating pleural drainage or persisting >7 days were reported to the German Surveillance Unit for Rare Diseases in Childhood between October 2010 and June 2017. All bacteria detected in blood or pleural fluid (by culture/PCR) were included, with serotyping for Streptococcus pneumoniae. Results The median age of all 1447 PPE/PE patients was 5 years (interquartile range 3-10). In 488 of the 1447 children with PPE/PE (34\%), 541 bacteria (>40 species) were detected. Aerobic gram-positive cocci accounted for 469 of 541 bacteria detected (87\%); these were most frequently Streptococcus pneumoniae (41\%), Streptococcus pyogenes (19\%) and Staphylococcus aureus (6\%). Serotype 3 accounted for 45\% of 78 serotyped S. pneumoniae strains. Annual PPE/PE incidence varied between 14 (95\%CI 12-16) and 18 (95\%CI 16-21) PPE/PE per million children. Incidence of S. pneumoniae PPE/PE decreased from 3.5 (95\%CI 2.5-4.6) per million children in 2010/11 to 1.5 (95\%CI 0.9-2.4) in 2013/14 (p 0.002), followed by a re-increase to 2.2 (95\%CI 1.5-3.2) by 2016/17 (p 0.205). Conclusions In the era of widespread PCV immunization, cases of paediatric PPE/PE were still caused mainly by S. pneumoniae and, increasingly, by S. pyogenes. The re-increase in the incidence of PPE/PE overall and in S. pneumoniae-associated PPE/PE indicates ongoing changes in the bacterial aetiology and requires further surveillance.},
  language  = {en}
}
@article{WeissZieglerFliesseretal.2018,
  author    = {Weiss, Esther and Ziegler, Sabrina and Fliesser, Mirjam and Schmitt, Anna-Lena and H{\"u}nniger, Kerstin and Kurzai, Oliver and Morton, Charles-Oliver and Einsele, Hermann and Loeffler, Juergen},
  title     = {First Insights in NK—DC Cross-Talk and the Importance of Soluble Factors During Infection With Aspergillus fumigatus},
  series = {Frontiers in Cellular and Infection Microbiology},
  volume    = {8},
  journal   = {Frontiers in Cellular and Infection Microbiology},
  doi       = {10.3389/fcimb.2018.00288},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-233565},
  year      = {2018},
  abstract  = {Invasive aspergillosis (IA) is an infectious disease caused by the fungal pathogen Aspergillus fumigatus that mainly affects immunocompromised hosts. To investigate immune cell cross-talk during infection with A. fumigatus, we co-cultured natural killer (NK) cells and dendritic cells (DC) after stimulation with whole fungal structures, components of the fungal cell wall, fungal lysate or ligands for distinct fungal receptors. Both cell types showed activation after stimulation with fungal components and were able to transfer activation signals to the counterpart not stimulated cell type. Interestingly, DCs recognized a broader spectrum of fungal components and thereby initiated NK cell activation when those did not recognize fungal structures. These experiments highlighted the supportive function of DCs in NK cell activation. Furthermore, we focused on soluble DC mediated NK cell activation and showed that DCs stimulated with the TLR2/Dectin-1 ligand zymosan could maximally stimulate the expression of CD69 on NK cells. Thus, we investigated the influence of both receptors for zymosan, Dectin-1 and TLR2, which are highly expressed on DCs but show only minimal expression on NK cells. Specific focus was laid on the question whether Dectin-1 or TLR2 signaling in DCs is important for the secretion of soluble factors leading to NK cell activation. Our results show that Dectin-1 and TLR2 are negligible for NK cell activation. We conclude that besides Dectin-1 and TLR2 other receptors on DCs are able to compensate for the missing signal.},
  language  = {en}
}
@article{KlotzHigginsSchaubmaretal.2019,
  author    = {Klotz, Peter and Higgins, Paul G. and Schaubmar, Andreas R. and Failing, Klaus and Leidner, Ursula and Seifert, Harald and Scheufen, Sandra and Semmler, Torsten and Ewers, Christa},
  title     = {Seasonal Occurrence and Carbapenem Susceptibility of Bovine Acinetobacter baumannii in Germany},
  series = {Frontiers in Microbiology},
  volume    = {10},
  journal   = {Frontiers in Microbiology},
  doi       = {10.3389/fmicb.2019.00272},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-325927},
  year      = {2019},
  abstract  = {Acinetobacter baumannii is one of the leading causes of nosocomial infections in humans. To investigate its prevalence, distribution of sequence types (STs), and antimicrobial resistance in cattle, we sampled 422 cattle, including 280 dairy cows, 59 beef cattle, and 83 calves over a 14-month period. Metadata, such as the previous use of antimicrobial agents and feeding, were collected to identify putative determining factors. Bacterial isolates were identified via MALDI-TOF/MS and PCR, antimicrobial susceptibility was evaluated via VITEK2 and antibiotic gradient tests, resistance genes were identified by PCR. Overall, 15.6\% of the cattle harbored A. baumannii, predominantly in the nose (60.3\% of the A. baumannii isolates). It was more frequent in dairy cows (21.1\%) than in beef cattle (6.8\%) and calves (2.4\%). A seasonal occurrence was shown with a peak between May and August. The rate of occurrence of A. baumannii was correlated with a history of use of 3rd generation cephalosporins in the last 6 months prior to sampling Multilocus sequence typing (Pasteur scheme) revealed 83 STs among 126 unique isolates. Nine of the bovine STs have previously been implicated in human infections. Besides known intrinsic resistance of the species, the isolates did not show additional resistance to the antimicrobial substances tested, including carbapenems. Our data suggest that cattle are not a reservoir for nosocomial A. baumannii but carry a highly diverse population of this species. Nevertheless, some STs seem to be able to colonize both cattle and humans.},
  language  = {en}
}
@phdthesis{Fohmann2024,
  author    = {Fohmann, Ingo},
  title     = {The Role of Sphingosine 1-phosphate and S1PR1-3 in the Pathophysiology of Meningococcal Meningitis},
  doi       = {10.25972/OPUS-36976},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-369764},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2024},
  abstract  = {Neisseria meningitidis (N. meningitidis) is an obligate human pathogen which causes live-threatening sepsis and meningitis. The fatality rate after meningococcal infection is high and surviving patients often suffer from severe sequelae. To cause meningitis, N. meningitidis must overcome the endothelium of the blood-brain barrier. The bacterium achieves this through the interaction with endothelial surface receptors leading to alternations of the cellular metabolism and signaling, which lastly results in cellular uptake and barrier traversal of N. meningitidis. Sphingosine 1-phosphate (S1P) is a lipid mediator that belongs to the class of sphingolipids and regulates the integrity of the blood-brain barrier through the interaction with its cognate receptors S1P receptors 1-3 (S1PR1-3). In this study, high performance liquid chromatography coupled with mass spectrometry (LC-MS/MS) was used to generate a time-resolved picture of the sphingolipid metabolism in a brain endothelial cell line (hCMEC/D3) upon meningococcal infection. Among various changes, S1P was elevated in the cellular compartment as well as in the supernatant of infected hCMEC/D3s. Analysis of mRNA expression in infected hCMEC/D3s with quantitative real-time polymerase chain reaction (RT-qPCR) revealed that the increase in S1P could be attributed to the enhanced expression of the S1P-generating enzyme sphingosine kinase 1 (SphK1). Antibody-based detection of SphK1 protein or phosphorylation at SphK1 residue Serine 225 in hCMEC/D3 plasma membrane fractions via Western Blot revealed that N. meningitidis also induced SphK1 phospho-activation and recruitment to the plasma membrane. Importantly, recruitment of SphK1 to the plasma membrane increases the probability of substrate encounter, thus elevating SphK activity. Enhanced SphK activity was also reflected on a functional level, as detected by a commercially available ATP depletion assay used for measuring the enzymatic activity of SphK. Infection of hCMEC/D3 cells with pilus-deficient mutants resulted in a lower SphK activation compared to the N. meningitidis wild type strain. hCMEC/D3 treatment with pilus-enriched protein fractions showed SphK activation similar to the infection with living bacteria and could be ascribed to pilus interaction with the membrane-proximal domain of cellular surface receptor CD147. Inhibition of SphK1 or SphK2 through pre-treatment with specific inhibitors or RNA interference reduced uptake of N. meningitidis into hCMEC/D3 cells, as measured with Gentamicin protection assays. Released S1P induced the phospho-activation of epidermal growth factor receptor (EGFR) via S1PR2 activation, whose expression was also increasing during infection. Furthermore, S1PR2 blockage had a preventive effect on bacterial invasion into hCMEC/D3 cells. On the contrary, activation of S1PR1+3 also reduced bacterial uptake, indicating an opposing regulatory role of S1PR1+3 and S1PR2 during N. meningitidis uptake. Moreover, SphK2 inhibition prevented inflammatory cytokine expression as well as release of interleukin-8 after N. meningitidis infection. Taken together, this study demonstrates the central role of S1P and its cognate receptors S1PR1-3 in the pathophysiology of meningococcal meningitis.},
  subject      = {Blut-Hirn-Schranke},
  language  = {en}
}
@article{KrausBrinkSiegel2019,
  author    = {Kraus, Amelie J. and Brink, Benedikt G. and Siegel, T. Nicolai},
  title     = {Efficient and specific oligo-based depletion of rRNA},
  series = {Scientific Reports},
  volume    = {9},
  journal   = {Scientific Reports},
  doi       = {10.1038/s41598-019-48692-2},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-224829},
  year      = {2019},
  abstract  = {In most organisms, ribosomal RNA (rRNA) contributes to >85\% of total RNA. Thus, to obtain useful information from RNA-sequencing (RNA-seq) analyses at reasonable sequencing depth, typically, mature polyadenylated transcripts are enriched or rRNA molecules are depleted. Targeted depletion of rRNA is particularly useful when studying transcripts lacking a poly(A) tail, such as some non-coding RNAs (ncRNAs), most bacterial RNAs and partially degraded or immature transcripts. While several commercially available kits allow effective rRNA depletion, their efficiency relies on a high degree of sequence homology between oligonucleotide probes and the target RNA. This restricts the use of such kits to a limited number of organisms with conserved rRNA sequences. In this study we describe the use of biotinylated oligos and streptavidin-coated paramagnetic beads for the efficient and specific depletion of trypanosomal rRNA. Our approach reduces the levels of the most abundant rRNA transcripts to less than 5\% with minimal off-target effects. By adjusting the sequence of the oligonucleotide probes, our approach can be used to deplete rRNAs or other abundant transcripts independent of species. Thus, our protocol provides a useful alternative for rRNA removal where enrichment of polyadenylated transcripts is not an option and commercial kits for rRNA are not available.},
  language  = {en}
}
@article{AlZabenMedyukhinaDietrichetal.2019,
  author    = {Al-Zaben, Naim and Medyukhina, Anna and Dietrich, Stefanie and Marolda, Alessandra and H{\"u}nniger, Kerstin and Kurzai, Oliver and Figge, Marc Thilo},
  title     = {Automated tracking of label-free cells with enhanced recognition of whole tracks},
  series = {Scientific Reports},
  volume    = {9},
  journal   = {Scientific Reports},
  doi       = {10.1038/s41598-019-39725-x},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-221093},
  year      = {2019},
  abstract  = {Migration and interactions of immune cells are routinely studied by time-lapse microscopy of in vitro migration and confrontation assays. To objectively quantify the dynamic behavior of cells, software tools for automated cell tracking can be applied. However, many existing tracking algorithms recognize only rather short fragments of a whole cell track and rely on cell staining to enhance cell segmentation. While our previously developed segmentation approach enables tracking of label-free cells, it still suffers from frequently recognizing only short track fragments. In this study, we identify sources of track fragmentation and provide solutions to obtain longer cell tracks. This is achieved by improving the detection of low-contrast cells and by optimizing the value of the gap size parameter, which defines the number of missing cell positions between track fragments that is accepted for still connecting them into one track. We find that the enhanced track recognition increases the average length of cell tracks up to 2.2-fold. Recognizing cell tracks as a whole will enable studying and quantifying more complex patterns of cell behavior, e.g. switches in migration mode or dependence of the phagocytosis efficiency on the number and type of preceding interactions. Such quantitative analyses will improve our understanding of how immune cells interact and function in health and disease.},
  language  = {en}
}
@article{DichtlKocForsteretal.2021,
  author    = {Dichtl, Karl and Koc, {\"O}zlem and Forster, Johannes and Scharf, Christina and Suerbaum, Sebastian and Andrassy, Joachim and Wagener, Johannes and Schroeder, Ines},
  title     = {An invasive infection caused by the thermophilic mold Talaromyces thermophilus},
  series = {Infection},
  volume    = {49},
  journal   = {Infection},
  number    = {6},
  issn      = {0300-8126},
  doi       = {10.1007/s15010-021-01648-z},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-308970},
  pages     = {1347-1353},
  year      = {2021},
  abstract  = {Background Increasing incidence of invasive infections caused by rare fungi was observed over the recent years. Case Here, we describe the first reported case of an infection caused by the thermophilic mold Talaromyces thermophilus. Cultivation and, hence, identification of this fastidious organism is challenging since standard incubation conditions are not sufficient. Retrospective analysis of patient samples and in vitro experiments demonstrated that testing for fungal antigens, i.e., the cell wall components galactomannan and β-1,3-D-glucan, is a promising tool.},
  language  = {en}
}
@article{SchreiberLohrBaltesetal.2023,
  author    = {Schreiber, Laura M. and Lohr, David and Baltes, Steffen and Vogel, Ulrich and Elabyad, Ibrahim A. and Bille, Maya and Reiter, Theresa and Kosmala, Aleksander and Gassenmaier, Tobias and Stefanescu, Maria R. and Kollmann, Alena and Aures, Julia and Schnitter, Florian and Pali, Mihaela and Ueda, Yuichiro and Williams, Tatiana and Christa, Martin and Hofmann, Ulrich and Bauer, Wolfgang and Gerull, Brenda and Zernecke, Alma and Erg{\"u}n, S{\"u}leyman and Terekhov, Maxim},
  title     = {Ultra-high field cardiac MRI in large animals and humans for translational cardiovascular research},
  series = {Frontiers in Cardiovascular Medicine},
  volume    = {10},
  journal   = {Frontiers in Cardiovascular Medicine},
  issn      = {2297-055X},
  doi       = {10.3389/fcvm.2023.1068390},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-317398},
  year      = {2023},
  abstract  = {A key step in translational cardiovascular research is the use of large animal models to better understand normal and abnormal physiology, to test drugs or interventions, or to perform studies which would be considered unethical in human subjects. Ultrahigh field magnetic resonance imaging (UHF-MRI) at 7 T field strength is becoming increasingly available for imaging of the heart and, when compared to clinically established field strengths, promises better image quality and image information content, more precise functional analysis, potentially new image contrasts, and as all in-vivo imaging techniques, a reduction of the number of animals per study because of the possibility to scan every animal repeatedly. We present here a solution to the dual use problem of whole-body UHF-MRI systems, which are typically installed in clinical environments, to both UHF-MRI in large animals and humans. Moreover, we provide evidence that in such a research infrastructure UHF-MRI, and ideally combined with a standard small-bore UHF-MRI system, can contribute to a variety of spatial scales in translational cardiovascular research: from cardiac organoids, Zebra fish and rodent hearts to large animal models such as pigs and humans. We present pilot data from serial CINE, late gadolinium enhancement, and susceptibility weighted UHF-MRI in a myocardial infarction model over eight weeks. In 14 pigs which were delivered from a breeding facility in a national SARS-CoV-2 hotspot, we found no infection in the incoming pigs. Human scanning using CINE and phase contrast flow measurements provided good image quality of the left and right ventricle. Agreement of functional analysis between CINE and phase contrast MRI was excellent. MRI in arrested hearts or excised vascular tissue for MRI-based histologic imaging, structural imaging of myofiber and vascular smooth muscle cell architecture using high-resolution diffusion tensor imaging, and UHF-MRI for monitoring free radicals as a surrogate for MRI of reactive oxygen species in studies of oxidative stress are demonstrated. We conclude that UHF-MRI has the potential to become an important precision imaging modality in translational cardiovascular research.},
  language  = {en}
}
@article{WeissGruendahlDeckertetal.2023,
  author    = {Weiß, Martin and Gr{\"u}ndahl, Marthe and Deckert, J{\"u}rgen and Eichner, Felizitas A. and Kohls, Mirjam and St{\"o}rk, Stefan and Heuschmann, Peter U. and Hein, Grit},
  title     = {Differential network interactions between psychosocial factors, mental health, and health-related quality of life in women and men},
  series = {Scientific Reports},
  volume    = {13},
  journal   = {Scientific Reports},
  organization    = {STAAB-COVID Study Group},
  doi       = {10.1038/s41598-023-38525-8},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-357858},
  year      = {2023},
  abstract  = {Psychosocial factors affect mental health and health-related quality of life (HRQL) in a complex manner, yet gender differences in these interactions remain poorly understood. We investigated whether psychosocial factors such as social support and personal and work-related concerns impact mental health and HRQL differentially in women and men during the first year of the COVID-19 pandemic. Between June and October 2020, the first part of a COVID-19-specific program was conducted within the "Characteristics and Course of Heart Failure Stages A-B and Determinants of Progression (STAAB)" cohort study, a representative age- and gender-stratified sample of the general population of W{\"u}rzburg, Germany. Using psychometric networks, we first established the complex relations between personal social support, personal and work-related concerns, and their interactions with anxiety, depression, and HRQL. Second, we tested for gender differences by comparing expected influence, edge weight differences, and stability of the networks. The network comparison revealed a significant difference in the overall network structure. The male (N = 1370) but not the female network (N = 1520) showed a positive link between work-related concern and anxiety. In both networks, anxiety was the most central variable. These findings provide further evidence that the complex interplay of psychosocial factors with mental health and HRQL decisively depends on gender. Our results are relevant for the development of gender-specific interventions to increase resilience in times of pandemic crisis.},
  language  = {en}
}
@article{HaederSchaeubleGehlenetal.2023,
  author    = {H{\"a}der, Antje and Sch{\"a}uble, Sascha and Gehlen, Jan and Thielemann, Nadja and Buerfent, Benedikt C. and Sch{\"u}ller, Vitalia and Hess, Timo and Wolf, Thomas and Schr{\"o}der, Julia and Weber, Michael and H{\"u}nniger, Kerstin and L{\"o}ffler, J{\"u}rgen and Vylkova, Slavena and Panagiotou, Gianni and Schumacher, Johannes and Kurzai, Oliver},
  title     = {Pathogen-specific innate immune response patterns are distinctly affected by genetic diversity},
  series = {Nature Communications},
  volume    = {14},
  journal   = {Nature Communications},
  doi       = {10.1038/s41467-023-38994-5},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-357441},
  year      = {2023},
  abstract  = {Innate immune responses vary by pathogen and host genetics. We analyze quantitative trait loci (eQTLs) and transcriptomes of monocytes from 215 individuals stimulated by fungal, Gram-negative or Gram-positive bacterial pathogens. We identify conserved monocyte responses to bacterial pathogens and a distinct antifungal response. These include 745 response eQTLs (reQTLs) and corresponding genes with pathogen-specific effects, which we find first in samples of male donors and subsequently confirm for selected reQTLs in females. reQTLs affect predominantly upregulated genes that regulate immune response via e.g., NOD-like, C-type lectin, Toll-like and complement receptor-signaling pathways. Hence, reQTLs provide a functional explanation for individual differences in innate response patterns. Our identified reQTLs are also associated with cancer, autoimmunity, inflammatory and infectious diseases as shown by external genome-wide association studies. Thus, reQTLs help to explain interindividual variation in immune response to infection and provide candidate genes for variants associated with a range of diseases.},
  language  = {en}
}
@article{DuskeClausKroneetal.2024,
  author    = {Duske, Helene and Claus, Heike and Krone, Manuel and L{\^a}m, Thi{\^e}n-Tr{\´i}},
  title     = {Prevalence of piperacillin/tazobactam resistance in invasive \(Haemophilus\) \(influenzae\) in Germany},
  series = {JAC-Antimicrobial Resistance},
  volume    = {6},
  journal   = {JAC-Antimicrobial Resistance},
  number    = {1},
  issn      = {2632-1823},
  doi       = {10.1093/jacamr/dlad148},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-350424},
  year      = {2024},
  abstract  = {Background Haemophilus influenzae (Hi) is a Gram-negative bacterium that may cause sepsis or meningitis, treatment of which mainly includes β-lactam antibiotics. Since 2019 EUCAST breakpoints for piperacillin/tazobactam have been available. Little is known about the prevalence and mechanisms of piperacillin/tazobactam resistance in Hi. Objectives To provide reliable prevalence data for piperacillin/tazobactam resistance in Hi in Germany, to evaluate different antibiotic susceptibility testing methods and to examine possible resistance mechanisms. Methods According to EUCAST breakpoints, the MIC for piperacillin/tazobactam resistance is >0.25 mg/L. All invasive Hi in Germany from 2019 were examined by gradient agar diffusion (GAD) for piperacillin/tazobactam susceptibility. Piperacillin/tazobactam broth microdilution (BMD), piperacillin GAD on tazobactam-containing agar [piperacillin GAD on Mueller-Hinton agar with horse blood (MH-F)/tazobactam) and piperacillin/tazobactam agar dilution (AD) were used for confirmation. Phenotypic testing was complemented by ftsI sequencing. Results Piperacillin/tazobactam GAD resulted in 2.9\% (21/726) resistant Hi. BMD did not confirm piperacillin/tazobactam resistance. Two strains were found resistant by AD, of which one was also resistant using piperacillin GAD on MH-F/tazobactam. Overall, we found two strains with a piperacillin/tazobactam MIC >0.25 mg/L in at least two different tests (0.3\%). Both were β-lactamase-producing amoxicillin/clavulanate-resistant with PBP3 mutations characterized as group III-like+. Relevant PBP3 mutations occurred in six strains without phenotypic piperacillin/tazobactam resistance. These mutations suggest a reduced efficacy of β-lactam antibiotics in these isolates. Conclusions Piperacillin/tazobactam resistance prevalence in invasive Hi is low in Germany. Reduced susceptibility was correlated with PBP3 mutations, in particular with group III mutations.},
  language  = {en}
}
@article{CucherMaricontiManciullietal.2023,
  author    = {Cucher, Marcela A. and Mariconti, Mara and Manciulli, Tommaso and Vola, Ambra and Rosenzvit, Mara C. and Brehm, Klaus and Kamenetzky, Laura and Brunetti, Enrico},
  title     = {Circulating small RNA profiling of patients with alveolar and cystic echinococcosis},
  series = {Biology},
  volume    = {12},
  journal   = {Biology},
  number    = {5},
  issn      = {2079-7737},
  doi       = {10.3390/biology12050715},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-319270},
  year      = {2023},
  abstract  = {Alveolar (AE) and cystic (CE) echinococcosis are two parasitic diseases caused by the tapeworms Echinococcus multilocularis and E. granulosus sensu lato (s. l.), respectively. Currently, AE and CE are mainly diagnosed by means of imaging techniques, serology, and clinical and epidemiological data. However, no viability markers that indicate parasite state during infection are available. Extracellular small RNAs (sRNAs) are short non-coding RNAs that can be secreted by cells through association with extracellular vesicles, proteins, or lipoproteins. Circulating sRNAs can show altered expression in pathological states; hence, they are intensively studied as biomarkers for several diseases. Here, we profiled the sRNA transcriptomes of AE and CE patients to identify novel biomarkers to aid in medical decisions when current diagnostic procedures are inconclusive. For this, endogenous and parasitic sRNAs were analyzed by sRNA sequencing in serum from disease negative, positive, and treated patients and patients harboring a non-parasitic lesion. Consequently, 20 differentially expressed sRNAs associated with AE, CE, and/or non-parasitic lesion were identified. Our results represent an in-depth characterization of the effect E. multilocularis and E. granulosus s. l. exert on the extracellular sRNA landscape in human infections and provide a set of novel candidate biomarkers for both AE and CE detection.},
  language  = {en}
}
@article{AbimannanSumathiKrishnarajasekharetal.2019,
  author    = {Abimannan, Nagarajan and Sumathi, G. and Krishnarajasekhar, O. R. and Sinha, Bhanu and Krishnan, Padma},
  title     = {Clonal Clusters and Virulence Factors of Methicillin-Resistant \(Staphylococcus\) \(Aureus\): Evidence for Community-Acquired Methicillin-Resistant \(Staphylococcus\) \(Aureus\) Infiltration into Hospital Settings in Chennai, South India},
  series = {Indian Journal of Medical Microbiology},
  volume    = {37},
  journal   = {Indian Journal of Medical Microbiology},
  number    = {3},
  doi       = {10.4103/ijmm.IJMM_18_271},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-226963},
  pages     = {326-336},
  year      = {2019},
  abstract  = {Background and Objective: Staphylococcus aureus is one of the major pathogens of nosocomial infections as wells as community-acquired (CA) infections worldwide. So far, large-scale comprehensive molecular and epidemiological characterisation of S. aureus from very diverse settings has not been carried out in India. The objective of this study is to evaluate the molecular, epidemiological and virulence characteristics of S. aureus in both community and hospital settings in Chennai, southern India. Methods: S. aureus isolates were obtained from four different groups (a) healthy individuals from closed community settings, (b) inpatients from hospitals, (c) outpatients from hospitals, representing isolates of hospital-community interface and (d) HIV-infected patients to define isolates associated with the immunocompromised. Antibiotic susceptibility testing, multiplex polymerase chain reactions for detection of virulence and resistance determinants, molecular typing including Staphylococcal cassette chromosome mec (SCCmec) and agr typing, were carried out. Sequencing-based typing was done using spa and multilocus sequence typing (MLST) methods. Clonal complexes (CC) of hospital and CA methicillin-resistant S. aureus (MRSA) were identified and compared for virulence and resistance. Results and Conclusion: A total of 769 isolates of S. aureus isolates were studied. The prevalence of MRSA was found to be 7.17\%, 81.67\%, 58.33\% and 22.85\% for groups a, b, c and d, respectively. Of the four SCCmec types (I, III, IV and V) detected, SCCmec V was found to be predominant. Panton-Valentine leucocidin toxin genes were detected among MRSA isolates harbouring SCCmec IV and V. A total of 78 spa types were detected, t657 being the most prevalent. 13 MLST types belonging to 9 CC were detected. CC1 (ST-772, ST-1) and CC8 (ST238, ST368 and ST1208) were found to be predominant among MRSA. CA-MRSA isolates with SCCmec IV and V were isolated from all study groups including hospitalised patients and were found to be similar by molecular tools. This shows that CA MRSA has probably infiltrated into the hospital settings.},
  language  = {en}
}
@phdthesis{Endres2024,
  author    = {Endres, Leo Maximilian},
  title     = {Development of multicellular \(in\) \(vitro\) models of the meningeal blood-CSF barrier to study \(Neisseria\) \(meningitidis\) infection},
  doi       = {10.25972/OPUS-34621},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-346216},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2024},
  abstract  = {Neisseria meningitidis (the meningococcus) is one of the major causes of bacterial meningitis, a life-threatening inflammation of the meninges. Traversal of the meningeal blood-cerebrospinal fluid barrier (mBCSFB), which is composed of highly specialized brain endothelial cells (BECs), and subsequent interaction with leptomeningeal cells (LMCs) are critical for disease progression. Due to the human-exclusive tropism of N. meningitidis, research on this complex host-pathogen interaction is mostly limited to in vitro studies. Previous studies have primarily used peripheral or immortalized BECs alone, which do not retain relevant barrier phenotypes in culture. To study meningococcal interaction with the mBCSFB in a physiologically more accurate context, BEC-LMC co-culture models were developed in this project using BEC-like cells derived from induced pluripotent stem cells (iBECs) or hCMEC/D3 cells in combination with LMCs derived from tumor biopsies. Distinct BEC and LMC layers as well as characteristic expression of cellular markers were observed using transmission electron microscopy (TEM) and immunofluorescence staining. Clear junctional expression of brain endothelial tight and adherens junction proteins was detected in the iBEC layer. LMC co-culture increased iBEC barrier tightness and stability over a period of seven days, as determined by sodium fluorescein (NaF) permeability and transendothelial electrical resistance (TEER). Infection experiments demonstrated comparable meningococcal adhesion and invasion of the BEC layer in all models tested, consistent with previously published data. While only few bacteria crossed the iBEC-LMC barrier initially, transmigration rates increased substantially over 24 hours, despite constant high TEER. After 24 hours of infection, deterioration of the barrier properties was observed including loss of TEER and altered expression of tight and adherens junction components. Reduced mRNA levels of ZO-1, claudin-5, and VE-cadherin were detected in BECs from all models. qPCR and siRNA knockdown data suggested that transcriptional downregulation of these genes was potentially but not solely mediated by Snail1. Immunofluorescence staining showed reduced junctional coverage of occludin, indicating N. meningitidis-induced post-transcriptional modulation of this protein, as previous studies have suggested. Together, these results suggest a potential combination of transcellular and paracellular meningococcal traversal of the mBCSFB, with the more accessible paracellular route becoming available upon barrier disruption after prolonged N. meningitidis infection. Finally, N. meningitidis induced cellular expression of pro-inflammatory cytokines and chemokines such as IL-8 in all mBCSFB models. Overall, the work described in this thesis highlights the usefulness of advanced in vitro models of the mBCSFB that mimic native physiology and exhibit relevant barrier properties to study infection with meningeal pathogens such as N. meningitidis.},
  subject      = {Bakterielle Hirnhautentz{\"u}ndung},
  language  = {en}
}
@article{MoremiClausVogeletal.2019,
  author    = {Moremi, Nyambura and Claus, Heike and Vogel, Ulrich and Mshana, Stephen E.},
  title     = {The role of patients and healthcare workers Staphylococcus aureus nasal colonization in occurrence of surgical site infection among patients admitted in two centers in Tanzania},
  series = {Antimicrobial Resistance \& Infection Control},
  volume    = {8},
  journal   = {Antimicrobial Resistance \& Infection Control},
  doi       = {10.1186/s13756-019-0554-y},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-224185},
  year      = {2019},
  abstract  = {Background Colonization with Staphylococcus aureus has been identified as a risk for subsequent occurrence of infection. This study investigated the relationship between S. aureus colonization of patients and healthcare workers (HCWs), and subsequent surgical site infections (SSI). Methods Between December 2014 and September 2015, a total of 930 patients and 143 HCWs were enrolled from the Bugando Medical Centre and Sekou Toure hospital in Mwanza, Tanzania. On admission and discharge nasal swabs, with an additional of wound swab for those who developed SSI were collected from patients whereas HCWs were swabbed once. Identification and antimicrobial susceptibility testing were done by VITEK-MS and VITEK-2, respectively. Detection of Panton Valentine leukocidin (PVL) and mecA genes was done by PCR. S. aureus isolates were further characterized by spa typing and Multi-Locus Sequence Typing (MLST). Results Among 930 patients screened for S. aureus on admission, 129 (13.9\%) were positive of which 5.4\% (7/129) were methicillin-resistant S. aureus (MRSA). Amongst 363 patients rescreened on discharge, 301 patients had been tested negative on admission of whom 29 (9.6\%) turned positive after their hospital stay. Three (10.3\%) of the 29 acquired S. aureus were MRSA. Inducible Clindamycin resistance occurred more often among acquired S. aureus isolates than among isolates from admission [34.5\% (10/29) vs. 17.1\% (22/129), P = 0.018]. S. aureus contributed to 21.1\% (n = 12) of the 57 cases of investigated SSIs among 536 patients followed. Seven out of eight S. aureus carriage/infection pairs had the same spa and sequence types. The previously reported dominant PVL-positive ST88 MRSA strain with spa type t690 was detected in patients and HCW. Conclusion A significant proportion of patients acquired S. aureus during hospitalization. The finding of more than 90\% of S. aureus SSI to be of endogenous source underscores the need of improving infection prevention and control measures including screening and decolonization of high risk patients.},
  language  = {en}
}
@article{StraubVollmerLametal.2022,
  author    = {Straub, Anton and Vollmer, Andreas and L{\^a}m, Thi{\^e}n-Tr{\´i} and Brands, Roman C. and Stapf, Maximilian and Scherf-Clavel, Oliver and Bittrich, Max and Fuchs, Andreas and K{\"u}bler, Alexander C. and Hartmann, Stefan},
  title     = {Evaluation of advanced platelet-rich fibrin (PRF) as a bio-carrier for ampicillin/sulbactam},
  series = {Clinical Oral Investigations},
  volume    = {26},
  journal   = {Clinical Oral Investigations},
  number    = {12},
  doi       = {10.1007/s00784-022-04663-y},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-324515},
  pages     = {7033-7044},
  year      = {2022},
  abstract  = {Objectives Mechanisms of wound healing are often impaired in patients with osteonecrosis of the jaw (ONJ). According to the guidelines for the treatment of this disease, early surgical intervention is indicated. However, surgery often faces complications such as wound healing disorders. The application of platelet-rich fibrin (PRF) after necrosectomy between bone and mucosa may constitute a promising approach to improve surgical results. An aspect that was not investigated until now is that PRF acts as a "bio-carrier" for antibiotics previously applied intravenously. Materials and methods We investigated the antimicrobial properties of PRF in 24 patients presenting ONJ undergoing systemic antibiosis with ampicillin/sulbactam. We measured the concentration of ampicillin/sulbactam in plasma and PRF and performed agar diffusion tests. Ampicillin/sulbactam was applied intravenously to the patient 10 minutes for blood sampling for PRF. No further incorporation of patients' blood or PRF product with antibiotic drugs was obtained. Four healthy patients served as controls. Results Our results revealed that PRF is highly enriched with ampicillin/sulbactam that is released to the environment. The antibiotic concentration in PRF was comparable to the plasma concentration of ampicillin/sulbactam. The inhibition zone (IZ) of PRF was comparable to the standard ampicillin/sulbactam discs used in sensitivity testing. Conclusions The results of our study demonstrated that PRF is a reliable bio-carrier for systemic applied antibiotics and exhibits a large antimicrobial effect. Clinical relevance We describe a clinically useful feature of PRF as a bio-carrier for antibiotics. Especially when applied to poorly perfused tissues and bone such as in ONJ, the local release of antibiotics can reduce wound healing disorders like infections.},
  language  = {en}
}
@phdthesis{Koike2023,
  author    = {Koike, Akito},
  title     = {Molekular und zellbiologischer Ansatz hin zu neuartigen Medikamenten gegen \(Echinococcus\) \(multilocularis\)},
  doi       = {10.25972/OPUS-28864},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-288649},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2023},
  abstract  = {Echinococcosis is an important zoonosis. The causative agent of Alveolar Echinococcosis (AE) is Echinococcus multilocularis. The treatment of human AE is limited to surgery and chemotherapy with albendazole (ABZ). However, ABZ works only parasitostatically and it needs to be taken for long periods, although it causes adverse side effects. Thus, development of new, parasiticidal drug with selective toxicity is required. Because undifferentiated stem cells of E. multilocularis play key role in its longevity and regenerative capacity, targeting stem cells is especially important. In vitro screening of protein kinases inhibitors demonstrated that human PIM kinases inhibitors have detrimental effects on E. multilocularis. Through yeast two hybrid assay, the interaction of parasite PIM kinase (EmPIM) and its CDC25 (EmCDC25) was indicated. Through in situ hybridization, expression of EmPIM in the stem cells was observed. Therefore, EmPim is likely to be a positive regulator of cell cycle progression, the same as human Pim1. In addition, 20 compounds against EmPIM were selected through in silico screening and synthesized. One of them has a detrimental effect on E.multilocularis comparable to human pan-PIM inhibitors, but has much weaker toxicity on human cell lines. Furthermore, triclabendazole (TCBZ) and its metabolite TCBZSX, which are approved for another flatworm disease, Fascioliasis were tried on E. multilocularis. With two stem cell markers, damage to stem cells by TCBZSX was shown. In addition, primary cells from treated vesicles never regenerated and the damage to stem cells proved to be irreversible. Our in silico screening method used in EmPIM research has potential to identify compounds which overcome the side effect problem in ABZ-based chemotherapy. On the other hand, it is expected that my research of TCBZ can lead to development of a practical parasiticidal chemotherapy by combining TCBZ, which damages stem cells, and ABZ, which damages differentiated cells.},
  subject      = {Bandw{\"u}rmer},
  language  = {en}
}
@article{NyawaleMoremiMohamedetal.2022,
  author    = {Nyawale, Helmut A. and Moremi, Nyambura and Mohamed, Mohamed and Njwalila, Johnson and Silago, Vitus and Krone, Manuel and Konje, Eveline T. and Mirambo, Mariam M. and Mshana, Stephen E.},
  title     = {High seroprevalence of SARS-CoV-2 in Mwanza, northwestern Tanzania: a population-based survey},
  series = {International Journal of Environmental Research and Public Health},
  volume    = {19},
  journal   = {International Journal of Environmental Research and Public Health},
  number    = {18},
  issn      = {1660-4601},
  doi       = {10.3390/ijerph191811664},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-288134},
  year      = {2022},
  abstract  = {The transmission of the SARS-CoV-2 virus, which causes COVID-19, has been documented worldwide. However, the evidence of the extent to which transmission has occurred in different countries is still to be established. Understanding the magnitude and distribution of SARS-CoV-2 through seroprevalence studies is important in designing control and preventive strategies in communities. This study investigated the seropositivity of the SARS-CoV-2 virus antibodies in the communities of three different districts in the Mwanza region, Tanzania. A household cross-sectional survey was conducted in September 2021 using the modified African Centre for Disease and Prevention (ACDC) survey protocol. A blood sample was obtained from one member of each of the selected households who consented to take part in the survey. Immunochromatographic rapid test kits were used to detect IgM and IgG SARS-CoV-2 antibodies, followed by descriptive data analysis. Overall, 805 participants were enrolled in the study with a median age of 35 (interquartile range (IQR):27-47) years. The overall SARS-CoV-2 seropositivity was 50.4\% (95\%CI: 46.9-53.8\%). The IgG and IgM seropositivity of the SARS-CoV-2 antibodies was 49.3\% and 7.2\%, respectively, with 6.1\% being both IgG and IgM seropositive. A history of runny nose (aOR: 1.84, 95\%CI: 1.03-3.5, p = 0.036), loss of taste (aOR: 1.84, 95\%CI: 1.12-4.48, p = 0.023), and living in Ukerewe (aOR: 3.55, 95\%CI: 1.68-7.47, p = 0.001) and Magu (aOR: 2.89, 95\%CI: 1.34-6.25, p= 0.007) were all independently associated with SARS-CoV-2 IgM seropositivity. Out of the studied factors, living in the Ukerewe district was independently associated with IgG seropositivity (aOR 1.29, CI 1.08-1.54, p = 0.004). Twenty months after the first case of COVID-19 in Tanzania, about half of the studied population in Mwanza was seropositive for SARS-CoV-2.},
  language  = {en}
}
@article{AldejohannWiesePosseltGastmeieretal.2022,
  author    = {Aldejohann, Alexander Maximilian and Wiese-Posselt, Miriam and Gastmeier, Petra and Kurzai, Oliver},
  title     = {Expert recommendations for prevention and management of Candida auris transmission},
  series = {Mycoses},
  volume    = {65},
  journal   = {Mycoses},
  number    = {6},
  doi       = {10.1111/myc.13445},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-318570},
  pages     = {590 -- 598},
  year      = {2022},
  abstract  = {Candida auris was first described as a yeast pathogen in 2009. Since then, the species has emerged worldwide. In contrast to most other Candida spp., C. auris frequently exhibits multi-drug resistance and is readily transmitted in hospital settings. While most detections so far are from colonised patients, C. auris does cause superficial and life-threatening invasive infections. During management of the first documented C. auris transmission in a German hospital, experts from the National Reference Centers for Invasive Fungal Infections (NRZMyk) and the National Reference Center for Surveillance of Nosocomial Infections screened available literature and integrated available knowledge on infection prevention and C. auris epidemiology and biology to enable optimal containment. Relevant recommendations developed during this process are summarised in this guidance document, intended to assist in management of C. auris transmission and potential outbreak situations. Rapid and effective measures to contain C. auris spread require a multi-disciplinary approach that includes clinical specialists of the affected unit, nursing staff, hospital hygiene, diagnostic microbiology, cleaning staff, hospital management and experts in diagnostic mycology / fungal infections. Action should be initiated in a step-wise process and relevant interventions differ between management of singular C. auris colonised / infected patients and detection of potential C. auris transmission or nosocomial outbreaks.},
  language  = {en}
}
@article{StrobelSickenbergerSchoenetal.2022,
  author    = {Strobel, Katharina and Sickenberger, Christina and Schoen, Christoph and Kneitz, Hermann and Kolb-M{\"a}urer, Annette and Goebeler, Matthias},
  title     = {Diagnosis and therapy of Mycobacterium marinum: a single-center 21-year retrospective analysis},
  series = {Journal der Deutschen Dermatologischen Gesellschaft},
  volume    = {20},
  journal   = {Journal der Deutschen Dermatologischen Gesellschaft},
  number    = {9},
  doi       = {10.1111/ddg.14847},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-318428},
  pages     = {1211 -- 1218},
  year      = {2022},
  abstract  = {Background and Objectives In Europe, infections with Mycobacterium (M.) marinum are rare. We conducted a retrospective single-center study to assess the clinical spectrum of M. marinum infection and its diagnosis, treatment and outcome under real-world conditions. Patients and Methods Eighteen patients presenting with M. marinum infections between 1998 and 2018 were identified in the data warehouse of the University Hospital W{\"u}rzburg and considered for detailed analysis. Results Twelve patients reported aquatic exposure. In 16/18 cases the upper extremities were affected. No invasive infections were detected. Mean time to diagnosis was 15 weeks. Histology revealed granulomatous inflammation in 14 patients while mycobacterial cultures were positive for M. marinum in 16 cases. Most patients received antibiotic monotherapy (14/18) while combination therapy was administered in four cases. Treatment (with a median duration of 10 weeks) was successful in 13 patients. Five patients were lost to follow-up. Conclusions Our retrospective analysis of M. marinum infections at a German tertiary referral center revealed a considerable diagnostic delay and the relevance of microbiological culture, PCR and histology for diagnosis. Monotherapy with clarithromycin (rather than doxycycline) appeared as a reasonable treatment option while immunosuppressed or -compromised patients and those with extended disease received combination therapy.},
  language  = {en}
}
@article{ForsterDichtlWagener2022,
  author    = {Forster, Johannes and Dichtl, Karl and Wagener, Johannes},
  title     = {Lower beta-1,3-D-glucan testing cut-offs increase sensitivity for non-albicans Candida species bloodstream infections},
  series = {Mycoses},
  volume    = {65},
  journal   = {Mycoses},
  number    = {5},
  doi       = {10.1111/myc.13421},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-276515},
  pages     = {500 -- 507},
  year      = {2022},
  abstract  = {Purpose Fungal biomarkers support early diagnosis of invasive fungal infections. In this study, we evaluated the impact of a recent update to the manufacturer-recommended cut-off for beta-1,3-D-glucan (BDG) testing (Fujifilm Wako BDG assay) on sensitivity and specificity for the detection of candidemia. Additionally, we compared the performance with tests for Candida antigen (Ag by Serion ELISA antigen Candida, Virion\Serion) and anti-mannan antibodies (Ab by Hemkit Candida IHA, Ravo Diagnostika). Methods Sera of 82 patients with candidemia, which were sampled with a maximum distance of ±14 days from the date of sampling of the corresponding positive blood cultures, were retrospectively analysed for BDG, Ag and Ab. Results of BDG testing were compared with results from sera of 129 patients with candidemia from a different hospital. Results Sensitivity of BDG testing (47\%) was higher than for Ag (17\%) or Ab (20\%). By combining Ag and Ab testing, sensitivity was raised to 32\%. Lowering the cut-off of BDG from 11 pg/ml to the newly recommended cut-off of 7 pg/ml resulted in a significant increase in sensitivity (47\% vs 58\%, p = .01 and 63\% vs 71\% p < .01). At both centres, the increase was significant in NAC but not in C. albicans candidemia. No significant effects on specificity were observed. Conclusion BDG testing outperformed Ag and Ab testing and its combination. Lowering the BDG cut-off had no significant impact on specificity. The increase in sensitivity can be mainly attributed to a gain in sensitivity for non-albicans Candida species bloodstream infections.},
  language  = {en}
}
@article{NieuwenhuizenEvans2022,
  author    = {Nieuwenhuizen, Natalie E. and Evans, Joanna C.},
  title     = {Cellular and molecular mechanisms in mycobacterial infection},
  series = {International Journal of Molecular Sciences},
  volume    = {23},
  journal   = {International Journal of Molecular Sciences},
  number    = {13},
  issn      = {1422-0067},
  doi       = {10.3390/ijms23137205},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-284370},
  year      = {2022},
  abstract  = {No abstract available},
  language  = {en}
}
@article{BauerConchaMendozaKreienbrocketal.2022,
  author    = {Bauer, Hannah and Concha Mendoza, Gustavo Andr{\´e}s and Kreienbrock, Lothar and Hartmann, Maria and Frickmann, Hagen and Kann, Simone},
  title     = {Prevalence of common diseases in Indigenous people in Colombia},
  series = {Tropical Medicine and Infectious Disease},
  volume    = {7},
  journal   = {Tropical Medicine and Infectious Disease},
  number    = {6},
  issn      = {2414-6366},
  doi       = {10.3390/tropicalmed7060109},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-278953},
  year      = {2022},
  abstract  = {The Indigenous tribe called the Wiwa lives retracted in the Sierra Nevada de Santa Marta, Colombia. Little is known about their health status and whether the health care system in place covers their needs. In 2017 and 2018, a permanent physician was in charge for the Wiwa. Diseases and complaints were registered, ranked, and classified with the ICD-10 coding. Datasets from the Indigenous health care provider Dusakawi, collected from local health points and health brigades travelling sporadically into the fields for short visits, were compared. Furthermore, a list of provided medication was evaluated regarding the recorded needs. The most common complaints found were respiratory, infectious and parasitic, and digestive diseases. The top ten diagnoses collected in the health points and in the health brigade datasets were similar, although with a different ranking. The available medication showed a basic coverage only, with a critical lack of treatment for many severe, chronic, and life-threatening diseases. Most of the detected diseases in the Indigenous population are avoidable by an improvement in health care access, an expansion of the provided medication, and an increase in knowledge, hygiene, and life standards.},
  language  = {en}
}
@article{KurotschkaTiedemannWolfetal.2021,
  author    = {Kurotschka, Peter Konstantin and Tiedemann, Elena and Wolf, Dominik and Thier, Nicola and Forster, Johannes and Liese, Johannes G. and Gagyor, Ildiko},
  title     = {Management of common infections in German primary care: a cross-sectional survey of knowledge and confidence among General Practitioners and outpatient pediatricians},
  series = {Antibiotics},
  volume    = {10},
  journal   = {Antibiotics},
  number    = {9},
  issn      = {2079-6382},
  doi       = {10.3390/antibiotics10091131},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-246272},
  year      = {2021},
  abstract  = {Outpatient antibiotic use is closely related to antimicrobial resistance and in Germany, almost 70\% of antibiotic prescriptions in human health are issued by primary care physicians (PCPs). The aim of this study was to explore PCPs, namely General Practitioners' (GPs) and outpatient pediatricians' (PDs) knowledge of guideline recommendations on rational antimicrobial treatment, the determinants of confidence in treatment decisions and the perceived need for training in this topic in a large sample of PCPs from southern Germany. Out of 3753 reachable PCPs, 1311 completed the survey (overall response rate = 34.9\%). Knowledge of guideline recommendations and perceived confidence in making treatment decisions were high in both GPs and PDs. The two highest rated influencing factors on prescribing decisions were reported to be guideline recommendations and own clinical experiences, hence patients' demands and expectations were judged as not influencing treatment decisions. The majority of physicians declared to have attended at least one specific training course on antibiotic use, yet almost all the participating PCPs declared to need more training on this topic. More studies are needed to explore how consultation-related and context-specific factors could influence antibiotic prescriptions in general and pediatric primary care in Germany beyond knowledge. Moreover, efforts should be undertaken to explore the training needs of PCPs in Germany, as this would serve the development of evidence-based educational interventions targeted to the improvement of antibiotic prescribing decisions rather than being focused solely on knowledge of guidelines.},
  language  = {en}
}
@article{WaltherZimmermannTheuersbacheretal.2021,
  author    = {Walther, Grit and Zimmermann, Anna and Theuersbacher, Johanna and Kaerger, Kerstin and Lilienfeld-Toal, Marie von and Roth, Mathias and Kampik, Daniel and Geerling, Gerd and Kurzai, Oliver},
  title     = {Eye infections caused by filamentous fungi: spectrum and antifungal susceptibility of the prevailing agents in Germany},
  series = {Journal of Fungi},
  volume    = {7},
  journal   = {Journal of Fungi},
  number    = {7},
  issn      = {2309-608X},
  doi       = {10.3390/jof7070511},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-241810},
  year      = {2021},
  abstract  = {Fungal eye infections can lead to loss of vision and blindness. The disease is most prevalent in the tropics, although case numbers in moderate climates are increasing as well. This study aimed to determine the dominating filamentous fungi causing eye infections in Germany and their antifungal susceptibility profiles in order to improve treatment, including cases with unidentified pathogenic fungi. As such, we studied all filamentous fungi isolated from the eye or associated materials that were sent to the NRZMyk between 2014 and 2020. All strains were molecularly identified and antifungal susceptibility testing according to the EUCAST protocol was performed for common species. In total, 242 strains of 66 species were received. Fusarium was the dominating genus, followed by Aspergillus, Purpureocillium, Alternaria, and Scedosporium. The most prevalent species in eye samples were Fusarium petroliphilum, F. keratoplasticum, and F. solani of the Fusarium solani species complex. The spectrum of species comprises less susceptible taxa for amphotericin B, natamycin, and azoles, including voriconazole. Natamycin is effective for most species but not for Aspergillus flavus or Purpureocillium spp. Some strains of F. solani show MICs higher than 16 mg/L. Our data underline the importance of species identification for correct treatment.},
  language  = {en}
}
@article{ZoranSeelbinderWhiteetal.2022,
  author    = {Zoran, Tamara and Seelbinder, Bastian and White, Philip Lewis and Price, Jessica Sarah and Kraus, Sabrina and Kurzai, Oliver and Linde, Joerg and H{\"a}der, Antje and Loeffler, Claudia and Grigoleit, Goetz Ulrich and Einsele, Hermann and Panagiotou, Gianni and Loeffler, Juergen and Sch{\"a}uble, Sascha},
  title     = {Molecular profiling reveals characteristic and decisive signatures in patients after allogeneic stem cell transplantation suffering from invasive pulmonary aspergillosis},
  series = {Journal of Fungi},
  volume    = {8},
  journal   = {Journal of Fungi},
  number    = {2},
  issn      = {2309-608X},
  doi       = {10.3390/jof8020171},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-262105},
  year      = {2022},
  abstract  = {Despite available diagnostic tests and recent advances, diagnosis of pulmonary invasive aspergillosis (IPA) remains challenging. We performed a longitudinal case-control pilot study to identify host-specific, novel, and immune-relevant molecular candidates indicating IPA in patients post allogeneic stem cell transplantation (alloSCT). Supported by differential gene expression analysis of six relevant in vitro studies, we conducted RNA sequencing of three alloSCT patients categorized as probable IPA cases and their matched controls without Aspergillus infection (66 samples in total). We additionally performed immunoassay analysis for all patient samples to gain a multi-omics perspective. Profiling analysis suggested LGALS2, MMP1, IL-8, and caspase-3 as potential host molecular candidates indicating IPA in investigated alloSCT patients. MMP1, IL-8, and caspase-3 were evaluated further in alloSCT patients for their potential to differentiate possible IPA cases and patients suffering from COVID-19-associated pulmonary aspergillosis (CAPA) and appropriate control patients. Possible IPA cases showed differences in IL-8 and caspase-3 serum levels compared with matched controls. Furthermore, we observed significant differences in IL-8 and caspase-3 levels among CAPA patients compared with control patients. With our conceptual work, we demonstrate the potential value of considering the human immune response during Aspergillus infection to identify immune-relevant molecular candidates indicating IPA in alloSCT patients. These human host candidates together with already established fungal biomarkers might improve the accuracy of IPA diagnostic tools.},
  language  = {en}
}
@article{StreckForstervonHertzbergBoelchetal.2022,
  author    = {Streck, Laura Elisa and Forster, Johannes and von Hertzberg-Boelch, Sebastian Philipp and Reichel, Thomas and Rudert, Maximilian and Rueckl, Kilian},
  title     = {The role of synovial fluid aspiration in shoulder joint infections},
  series = {BMC Musculoskeletal Disorders},
  volume    = {23},
  journal   = {BMC Musculoskeletal Disorders},
  doi       = {10.1186/s12891-022-05285-x},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-300795},
  year      = {2022},
  abstract  = {Background Joint aspiration with analysis of synovial fluid white blood cell count (WBC) and microbiological culture is a widely established aspect in the diagnosis of shoulder joint infections (SJI). In case of a two stage revision for SJI, joint aspiration before re-/implantation of a total shoulder arthroplasty (TSA) was used to rule out persistent infection for years but its value is under debate. Shoulder specific data on all aspects is rare. The current study aims to answer the following research questions: Does joint aspiration have an insufficient predictive value in the diagnosis of SJI in (1) initial workup and (2) before definite arthroplasty with polymethylmethacrylate (PMMA)-Spacer in place? Methods This retrospective evaluation investigates 35 patients that were treated for SJI with a two staged implantation of a TSA after debridement and implantation of an PMMA-Spacer. Joint aspirations were performed preoperatively (PA) and before re-/implantation of the prosthesis while spacer was in place (interstage aspiration, IA). Samples were taken for microbiological culture and analysis of WBC. Sensitivity and specificity were calculated with reference to intraoperative microbiological samples. Receiver Operating Characteristic (ROC), Area-Under-Curve analysis (AUC) and calculation of the Youden index were performed to find optimum cut-off for WBC. Results The sensitivity of microbiological cultures from PA was 58.3\% and the specificity was 88.9\%. The mean WBC was 27,800 leucocytes/mm3 (range 400-96,300). The maximum Youden index (0.857) was a cut-off of 2600 leucocytes/mm3 with a sensitivity of 85.7\% and a specificity of 100.0\%. The sensitivity and specificity of IA were 0.0\% and 88.5\%, respectively. Conclusions Preoperative aspiration is likely to miss Cutibacteria spp. and CoNS and cannot rule out infection for sure. However, we recommend it for its advantages of targeted antibiotic therapy in case of germ identification. Empiric antibiotic therapy should cover Cutibacteria and CoNS even if aspiration showed negative microbiological cultures. In contrast, the diagnostic value of interstage aspiration does not qualify for its routine use.},
  language  = {en}
}
@article{SoundararajanMarincolaLiongetal.2023,
  author    = {Soundararajan, Manonmani and Marincola, Gabriella and Liong, Olivia and Marciniak, Tessa and Wencker, Freya D. R. and Hofmann, Franka and Schollenbruch, Hannah and Kobusch, Iris and Linnemann, Sabrina and Wolf, Silver A. and Helal, Mustafa and Semmler, Torsten and Walther, Birgit and Schoen, Christoph and Nyasinga, Justin and Revathi, Gunturu and Boelhauve, Marc and Ziebuhr, Wilma},
  title     = {Farming practice influences antimicrobial resistance burden of non-aureus staphylococci in pig husbandries},
  series = {Microorganisms},
  volume    = {11},
  journal   = {Microorganisms},
  number    = {1},
  issn      = {2076-2607},
  doi       = {10.3390/microorganisms11010031},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-312750},
  year      = {2023},
  abstract  = {Non-aureus staphylococci (NAS) are ubiquitous bacteria in livestock-associated environments where they may act as reservoirs of antimicrobial resistance (AMR) genes for pathogens such as Staphylococcus aureus. Here, we tested whether housing conditions in pig farms could influence the overall AMR-NAS burden. Two hundred and forty porcine commensal and environmental NAS isolates from three different farm types (conventional, alternative, and organic) were tested for phenotypic antimicrobial susceptibility and subjected to whole genome sequencing. Genomic data were analysed regarding species identity and AMR gene carriage. Seventeen different NAS species were identified across all farm types. In contrast to conventional farms, no AMR genes were detectable towards methicillin, aminoglycosides, and phenicols in organic farms. Additionally, AMR genes to macrolides and tetracycline were rare among NAS in organic farms, while such genes were common in conventional husbandries. No differences in AMR detection existed between farm types regarding fosfomycin, lincosamides, fusidic acid, and heavy metal resistance gene presence. The combined data show that husbandry conditions influence the occurrence of resistant and multidrug-resistant bacteria in livestock, suggesting that changing husbandry practices may be an appropriate means of limiting the spread of AMR bacteria on farms.},
  language  = {en}
}
@article{StraubStapfFischeretal.2022,
  author    = {Straub, Anton and Stapf, Maximilian and Fischer, Markus and Vollmer, Andreas and Linz, Christian and L{\^a}m, Thi{\^e}n-Tr{\´i} and K{\"u}bler, Alexander and Brands, Roman C. and Scherf-Clavel, Oliver and Hartmann, Stefan},
  title     = {Bone concentration of ampicillin/sulbactam: a pilot study in patients with osteonecrosis of the jaw},
  series = {International Journal of Environmental Research and Public Health},
  volume    = {19},
  journal   = {International Journal of Environmental Research and Public Health},
  number    = {22},
  issn      = {1660-4601},
  doi       = {10.3390/ijerph192214917},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-297413},
  year      = {2022},
  abstract  = {Osteonecrosis of the jaw (ONJ) occurs typically after irradiation of the head and neck area or after the intake of antiresorptive agents. Both interventions can lead to compromised bone perfusion and can ultimately result in infection and necrosis. Treatment usually consists of surgical necrosectomy and prolonged antibiotic therapy, usually through beta-lactams such as ampicillin/sulbactam. The poor blood supply in particular raises the question as to whether this form of antibiosis can achieve sufficient concentrations in the bone. Therefore, we investigated the antibiotic concentration in plasma and bone samples in a prospective study. Bone samples were collected from the necrosis core and in the vital surrounding bone. The measured concentrations in plasma for ampicillin and sulbactam were 126.3 ± 77.6 and 60.2 ± 35.0 µg/mL, respectively. In vital bone and necrotic bone samples, the ampicillin/sulbactam concentrations were 6.3 ± 7.8/1.8 ± 2.0 µg/g and 4.9 ± 7.0/1.7 ± 1.7 µg/g, respectively. These concentrations are substantially lower than described in the literature. However, the concentration seems sufficient to kill most bacteria, such as Streptococci and Staphylococci, which are mostly present in the biofilm of ONJ. We, therefore, conclude that intravenous administration of ampicillin/sulbactam remains a valuable treatment in the therapy of ONJ. Nevertheless, increasing resistance of Escherichia coli towards beta-lactam antibiotics have been reported and should be considered.},
  language  = {en}
}
@article{TappeLauruschkatStrobeletal.2022,
  author    = {Tappe, Beeke and Lauruschkat, Chris D. and Strobel, Lea and Pantale{\´o}n Garc{\´i}a, Jezreel and Kurzai, Oliver and Rebhan, Silke and Kraus, Sabrina and Pfeuffer-Jovic, Elena and Bussemer, Lydia and Possler, Lotte and Held, Matthias and H{\"u}nniger, Kerstin and Kniemeyer, Olaf and Sch{\"a}uble, Sascha and Brakhage, Axel A. and Panagiotou, Gianni and White, P. Lewis and Einsele, Hermann and L{\"o}ffler, J{\"u}rgen and Wurster, Sebastian},
  title     = {COVID-19 patients share common, corticosteroid-independent features of impaired host immunity to pathogenic molds},
  series = {Frontiers in Immunology},
  volume    = {13},
  journal   = {Frontiers in Immunology},
  issn      = {1664-3224},
  doi       = {10.3389/fimmu.2022.954985},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-283558},
  year      = {2022},
  abstract  = {Patients suffering from coronavirus disease-2019 (COVID-19) are susceptible to deadly secondary fungal infections such as COVID-19-associated pulmonary aspergillosis and COVID-19-associated mucormycosis. Despite this clinical observation, direct experimental evidence for severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2)-driven alterations of antifungal immunity is scarce. Using an ex-vivo whole blood stimulation assay, we challenged blood from twelve COVID-19 patients with Aspergillus fumigatus and Rhizopus arrhizus antigens and studied the expression of activation, maturation, and exhaustion markers, as well as cytokine secretion. Compared to healthy controls, T-helper cells from COVID-19 patients displayed increased expression levels of the exhaustion marker PD-1 and weakened A. fumigatus- and R. arrhizus-induced activation. While baseline secretion of proinflammatory cytokines was massively elevated, whole blood from COVID-19 patients elicited diminished release of T-cellular (e.g., IFN-γ, IL-2) and innate immune cell-derived (e.g., CXCL9, CXCL10) cytokines in response to A. fumigatus and R. arrhizus antigens. Additionally, samples from COVID-19 patients showed deficient granulocyte activation by mold antigens and reduced fungal killing capacity of neutrophils. These features of weakened anti-mold immune responses were largely decoupled from COVID-19 severity, the time elapsed since diagnosis of COVID-19, and recent corticosteroid uptake, suggesting that impaired anti-mold defense is a common denominator of the underlying SARS-CoV-2 infection. Taken together, these results expand our understanding of the immune predisposition to post-viral mold infections and could inform future studies of immunotherapeutic strategies to prevent and treat fungal superinfections in COVID-19 patients.},
  language  = {en}
}
@article{RohdeHimmelHofingeretal.2022,
  author    = {Rohde, J{\"o}rn and Himmel, Wolfgang and Hofinger, Clemens and L{\^a}m, Thi{\^e}n-Tr{\´i} and Schrader, Hanna and Wallstabe, Julia and Kurzai, Oliver and G{\´a}gyor, Ildik{\´o}},
  title     = {Diagnostic accuracy and feasibility of a rapid SARS-CoV-2 antigen test in general practice - a prospective multicenter validation and implementation study},
  series = {BMC Primary Care},
  volume    = {23},
  journal   = {BMC Primary Care},
  number    = {1},
  doi       = {10.1186/s12875-022-01756-1},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-299659},
  year      = {2022},
  abstract  = {Background PCR testing is considered the gold standard for SARS-CoV-2 diagnosis but its results are earliest available hours to days after testing. Rapid antigen tests represent a diagnostic tool enabling testing at the point of care. Rapid antigen tests have mostly been validated by the manufacturer or in controlled laboratory settings only. External validation at the point of care, particularly in general practice where the test is frequently used, is needed. Furthermore, it is unclear how well point of care tests are accepted by the practice staff. Methods In this prospective multicenter validation study in primary care, general practitioners included adult individuals presenting with symptoms suggesting COVID-19. Each patient was tested by the general practitioner, first with a nasopharyngeal swab for the point of care test (Roche SARS-CoV-2 Rapid Antigen Test) and then with a second swab for PCR testing. Using the RT-PCR result as a reference, we calculated specificity, sensitivity, positive predictive value and negative predictive value, with their 95\% confidence intervals. General practitioners and medical assistants completed a survey to assess feasibility and usefulness of the point of care tests. Results In 40 practices in W{\"u}rzburg, Germany, 1518 patients were recruited between 12/2020 and 06/2021. The point of care test achieved a sensitivity of 78.3\% and a specificity of 99.5\% compared to RT-PCR. With a prevalence of 9.5\%, the positive predictive value was 93.9\% and the negative predictive value was 97.8\%. General practitioners rated the point of care test as a helpful tool to support diagnostics in patients with signs and symptoms suggestive for infection, particularly in situations where decision on further care is needed at short notice. Conclusion The point of care test used in this study showed a sensitivity below the manufacturer's specification (Sensitivity 96.25\%) in the practice but high values for specificity and high positive predictive value and negative predictive value. Although widely accepted in the practice, measures for further patient management require a sensitive interpretation of the point of care test results.},
  language  = {en}
}
@article{ForsterKohlmorgenHaasetal.2022,
  author    = {Forster, Johannes and Kohlmorgen, Britta and Haas, Julian and Weis, Philipp and Breunig, Lukas and Turnwald, Doris and Mizaikoff, Boris and Schoen, Christoph},
  title     = {A streamlined method for the fast and cost-effective detection of bacterial pathogens from positive blood cultures for the BacT/ALERT blood culture system using the Vitek MS mass spectrometer},
  series = {PLoS ONE},
  volume    = {17},
  journal   = {PLoS ONE},
  number    = {4},
  doi       = {10.1371/journal.pone.0267669},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-300213},
  year      = {2022},
  abstract  = {Background and objective Prompt pathogen identification of blood stream infections is essential to provide appropriate antibiotic treatment. Therefore, the objective of this prospective single centre study was to establish an inexpensive, fast and accurate protocol for bacterial species identification with SDS protein-extraction directly from BacT/Alert® blood culture (BC) bottles by VitekMS®. Results Correct species identification was obtained for 198/266 (74.4\%, 95\%-CI = [68.8\%, 79.6\%]) of pathogens. The protocol was more successful in identifying 87/96 (91.4\%, 95\%-CI = [83.8\%, 93.2\%]) gram-negative bacteria than 110/167 (65.9\%, 95\%-CI = [58.1\%, 73.0\%]) gram-positive bacteria. The hands-on time for sample preparation and measurement was about 15 min for up to five samples. This is shorter than for most other protocols using a similar lysis-centrifugation approach for the combination of BacT/Alert® BC bottles and the Vitek® MS mass spectrometer. The estimated costs per sample were approx. 1.80€ which is much cheaper than for commercial kits. Conclusion This optimized protocol allows for accurate identification of bacteria directly from blood culture bottles for laboratories equipped with BacT/Alert® blood culture bottles and VitekMS® mass spectrometer.},
  language  = {en}
}
@article{EndresJungblutDivyapicigiletal.2022,
  author    = {Endres, Leo M. and Jungblut, Marvin and Divyapicigil, Mustafa and Sauer, Markus and Stigloher, Christian and Christodoulides, Myron and Kim, Brandon J. and Schubert-Unkmeir, Alexandra},
  title     = {Development of a multicellular in vitro model of the meningeal blood-CSF barrier to study Neisseria meningitidis infection},
  series = {Fluids and Barriers of the CNS},
  volume    = {19},
  journal   = {Fluids and Barriers of the CNS},
  number    = {1},
  doi       = {10.1186/s12987-022-00379-z},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-300208},
  year      = {2022},
  abstract  = {Background Bacterial meningitis is a life-threatening disease that occurs when pathogens such as Neisseria meningitidis cross the meningeal blood cerebrospinal fluid barrier (mBCSFB) and infect the meninges. Due to the human-specific nature of N. meningitidis, previous research investigating this complex host-pathogen interaction has mostly been done in vitro using immortalized brain endothelial cells (BECs) alone, which often do not retain relevant barrier properties in culture. Here, we developed physiologically relevant mBCSFB models using BECs in co-culture with leptomeningeal cells (LMCs) to examine N. meningitidis interaction. Methods We used BEC-like cells derived from induced pluripotent stem cells (iBECs) or hCMEC/D3 cells in co-culture with LMCs derived from tumor biopsies. We employed TEM and structured illumination microscopy to characterize the models as well as bacterial interaction. We measured TEER and sodium fluorescein (NaF) permeability to determine barrier tightness and integrity. We then analyzed bacterial adherence and penetration of the cell barrier and examined changes in host gene expression of tight junctions as well as chemokines and cytokines in response to infection. Results Both cell types remained distinct in co-culture and iBECs showed characteristic expression of BEC markers including tight junction proteins and endothelial markers. iBEC barrier function as determined by TEER and NaF permeability was improved by LMC co-culture and remained stable for seven days. BEC response to N. meningitidis infection was not affected by LMC co-culture. We detected considerable amounts of BEC-adherent meningococci and a relatively small number of intracellular bacteria. Interestingly, we discovered bacteria traversing the BEC-LMC barrier within the first 24 h post-infection, when barrier integrity was still high, suggesting a transcellular route for N. meningitidis into the CNS. Finally, we observed deterioration of barrier properties including loss of TEER and reduced expression of cell-junction components at late time points of infection. Conclusions Here, we report, for the first time, on co-culture of human iPSC derived BECs or hCMEC/D3 with meningioma derived LMCs and find that LMC co-culture improves barrier properties of iBECs. These novel models allow for a better understanding of N. meningitidis interaction at the mBCSFB in a physiologically relevant setting.},
  language  = {en}
}
@article{RufBrantlWagener2018,
  author    = {Ruf, Dominik and Brantl, Victor and Wagener, Johannes},
  title     = {Mitochondrial Fragmentation in \(Aspergillus\) \(fumigatus\) as Early Marker of Granulocyte Killing Activity},
  series = {Frontiers in Cellular and Infection Microbiology},
  volume    = {8},
  journal   = {Frontiers in Cellular and Infection Microbiology},
  number    = {128},
  doi       = {10.3389/fcimb.2018.00128},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-227133},
  year      = {2018},
  abstract  = {The host's defense against invasive mold infections relies on diverse antimicrobial activities of innate immune cells. However, studying these mechanisms in vitro is complicated by the filamentous nature of such pathogens that typically form long, branched, multinucleated and compartmentalized hyphae. Here we describe a novel method that allows for the visualization and quantification of the antifungal killing activity exerted by human granulocytes against hyphae of the opportunistic pathogen Aspergillus fumigatus. The approach relies on the distinct impact of fungal cell death on the morphology of mitochondria that were visualized with green fluorescent protein (GFP). We show that oxidative stress induces complete fragmentation of the tubular mitochondrial network which correlates with cell death of affected hyphae. Live cell microscopy revealed a similar and non-reversible disruption of the mitochondrial morphology followed by fading of fluorescence in Aspergillus hyphae that were killed by human granulocytes. Quantitative microscopic analysis of fixed samples was subsequently used to estimate the antifungal activity. By utilizing this assay, we demonstrate that lipopolysaccharides as well as human serum significantly increase the killing efficacy of the granulocytes. Our results demonstrate that evaluation of the mitochondrial morphology can be utilized to assess the fungicidal activity of granulocytes against A. fumigatus hyphae.},
  language  = {en}
}
@article{StreckGaalForsteretal.2021,
  author    = {Streck, Laura Elisa and Gaal, Chiara and Forster, Johannes and Konrads, Christian and Hertzberg-Boelch, Sebastian Philipp von and Rueckl, Kilian},
  title     = {Defining a synovial fluid white blood cell count threshold to predict periprosthetic infection after shoulder arthroplasty},
  series = {Journal of Clinical Medicine},
  volume    = {11},
  journal   = {Journal of Clinical Medicine},
  number    = {1},
  issn      = {2077-0383},
  doi       = {10.3390/jcm11010050},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-252275},
  year      = {2021},
  abstract  = {Background: The diagnosis of periprosthetic shoulder infection (PSI) requires a thorough diagnostic workup. Synovial fluid aspiration has been proven to be a reliable tool in the diagnosis of joint infections of the lower extremity, but shoulder specific data is limited. This study defines a threshold for synovial fluid white blood cell count (WBC) and assesses the reliability of microbiological cultures. Methods: Retrospective study of preoperative and intraoperative fluid aspiration of 31 patients who underwent a revision of a shoulder arthroplasty (15 with PSI defined by IDSA criteria, 16 without infection). The threshold for WBC was calculated by ROC/AUC analysis. Results: WBC was significantly higher in patients with PSI than in other patients. A threshold of 2800 leucocytes/mm\(^3\) showed a sensitivity of 87\% and a specificity of 88\% (AUROC 0.92). Microbiological cultures showed a sensitivity of 76\% and a specificity of 100\%. Conclusions: A threshold of 2800 leucocytes/mm\(^3\) in synovial fluid can be recommended to predict PSI. Microbiological culture has an excellent specificity and allows for targeted antibiotic therapy. Joint aspiration presents an important pillar to diagnose PSI.},
  language  = {en}
}
@article{SpringerHeldMengolietal.2021,
  author    = {Springer, Jan and Held, J{\"u}rgen and Mengoli, Carlo and Schlegel, Paul Gerhardt and Gamon, Florian and Tr{\"a}ger, Johannes and Kurzai, Oliver and Einsele, Hermann and Loeffler, Juergen and Eyrich, Matthias},
  title     = {Diagnostic performance of (1→3)-β-D-glucan alone and in combination with aspergillus PCR and galactomannan in serum of pediatric patients after allogeneic hematopoietic stem cell transplantation},
  series = {Journal of Fungi},
  volume    = {7},
  journal   = {Journal of Fungi},
  number    = {3},
  issn      = {2309-608X},
  doi       = {10.3390/jof7030238},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-234179},
  year      = {2021},
  abstract  = {Data on biomarker-assisted diagnosis of invasive aspergillosis (IA) in pediatric patients is scarce. Therefore, we conducted a cohort study over two years including 404 serum specimens of 26 pediatric patients after allogeneic hematopoietic stem cell transplantation (alloSCT). Sera were tested prospectively twice weekly for Aspergillus-specific DNA, galactomannan (GM), and retrospectively for (1→3)-β-D-glucan (BDG). Three probable IA and two possible invasive fungal disease (IFD) cases were identified using the European Organization for Research and Treatment of Cancer and the Mycoses Study Group (EORTC/MSGERC) 2019 consensus definitions. Sensitivity and specificity for diagnosis of probable IA and possible IFD was 80\% (95\% confidential interval (CI): 28-99\%) and 55\% (95\% CI: 32-77\%) for BDG, 40\% (95\% CI: 5-85\%) and 100\% (95\% CI: 83-100\%) for GM, and 60\% (95\% CI: 15-95\%) and 95\% (95\% CI: 75-100\%) for Aspergillus-specific real-time PCR. However, sensitivities have to be interpreted with great caution due to the limited number of IA cases. Interestingly, the low specificity of BDG was largely caused by false-positive BDG results that clustered around the date of alloSCT. The following strategies were able to increase BDG specificity: two consecutive positive BDG tests for diagnosis (specificity 80\% (95\% CI: 56-94\%)); using an optimized cutoff value of 306 pg/mL (specificity 90\% (95\% CI: 68-99\%)) and testing BDG only after the acute posttransplant phase. In summary, BDG can help to diagnose IA in pediatric alloSCT recipients. However, due to the poor specificity either an increased cutoff value should be utilized or BDG results should be confirmed by an alternative Aspergillus assay.},
  language  = {en}
}
@article{SattlerNosterBrunkeetal.2021,
  author    = {Sattler, Janko and Noster, Janina and Brunke, Anne and Plum, Georg and Wiegel, Pia and Kurzai, Oliver and Meis, Jacques F. and Hamprecht, Axel},
  title     = {Comparison of two commercially available qPCR kits for the detection of Candida auris},
  series = {Journal of Fungi},
  volume    = {7},
  journal   = {Journal of Fungi},
  number    = {2},
  issn      = {2309-608X},
  doi       = {10.3390/jof7020154},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-228879},
  year      = {2021},
  abstract  = {Candida auris is an emerging pathogen with resistance to many commonly used antifungal agents. Infections with C. auris require rapid and reliable detection methods to initiate successful medical treatment and contain hospital outbreaks. Conventional identification methods are prone to errors and can lead to misidentifications. PCR-based assays, in turn, can provide reliable results with low turnaround times. However, only limited data are available on the performance of commercially available assays for C. auris detection. In the present study, the two commercially available PCR assays AurisID (OLM, Newcastle Upon Tyne, UK) and Fungiplex Candida Auris RUO Real-Time PCR (Bruker, Bremen, Germany) were challenged with 29 C. auris isolates from all five clades and eight other Candida species as controls. AurisID reliably detected C. auris with a limit of detection (LoD) of 1 genome copies/reaction. However, false positive results were obtained with high DNA amounts of the closely related species C. haemulonii, C. duobushaemulonii and C. pseudohaemulonii. The Fungiplex Candida Auris RUO Real-Time PCR kit detected C. auris with an LoD of 9 copies/reaction. No false positive results were obtained with this assay. In addition, C. auris could also be detected in human blood samples spiked with pure fungal cultures by both kits. In summary, both kits could detect C. auris-DNA at low DNA concentrations but differed slightly in their limits of detection and specificity.},
  language  = {en}
}
@article{ApsemidouFuellerIdelevichetal.2020,
  author    = {Apsemidou, Athanasia and F{\"u}ller, Miriam Antonie and Idelevich, Evgeny A. and Kurzai, Oliver and Tragiannidis, Athanasios and Groll, Andreas H.},
  title     = {Candida lusitaniae breakthrough fungemia in an immuno-compromised adolescent: case report and review of the literature},
  series = {Journal of Fungi},
  volume    = {6},
  journal   = {Journal of Fungi},
  number    = {4},
  issn      = {2309-608X},
  doi       = {10.3390/jof6040380},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-220125},
  year      = {2020},
  abstract  = {Candida lusitaniae is a rare cause of candidemia that is known for its unique capability to rapidly acquire resistance to amphotericin B. We report the case of an adolescent with grade IV graft-vs.-host disease after hematopoietic cell transplantation who developed catheter-associated C. lusitaniae candidemia while on therapeutic doses of liposomal amphotericin B. We review the epidemiology of C. lusitaniae bloodstream infections in adult and pediatric patients, the development of resistance, and its role in breakthrough candidemia. Appropriate species identification, in vitro susceptibility testing, and source control are pivotal to optimal management of C. lusitaniae candidemia. Initial antifungal therapy may consist of an echinocandin and be guided by in vitro susceptibility and clinical response.},
  language  = {en}
}
@article{DichtlForsterOrmannsetal.2020,
  author    = {Dichtl, Karl and Forster, Johannes and Ormanns, Steffen and Horns, Heidi and Suerbaum, Sebastian and Seybold, Ulrich and Wagener, Johannes},
  title     = {Comparison of β-D-Glucan and galactomannan in serum for detection of invasive aspergillosis: retrospective analysis with focus on early diagnosis},
  series = {Journal of Fungi},
  volume    = {6},
  journal   = {Journal of Fungi},
  number    = {4},
  issn      = {2309-608X},
  doi       = {10.3390/jof6040253},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-216298},
  year      = {2020},
  abstract  = {The early diagnosis of invasive aspergillosis (IA) relies mainly on computed tomography imaging and testing for fungal biomarkers such as galactomannan (GM). We compared an established ELISA for the detection of GM with a turbidimetric assay for detection of the panfungal biomarker β-D-glucan (BDG) for early diagnosis of IA. A total of 226 serum specimens from 47 proven and seven probable IA cases were analysed. Sensitivity was calculated for samples obtained closest to the day of IA-diagnosis (d0). Additional analyses were performed by including samples obtained during the presumed course of disease. Most IA cases involved the respiratory system (63\%), and Aspergillus fumigatus was the most frequently isolated species (59\%). For proven cases, sensitivity of BDG/GM analysis was 57\%/40\%. Including all samples dating from -6 to +1 weeks from d0 increased sensitivities to 74\%/51\%. Sensitivity of BDG testing was as high as or higher than GM testing for all subgroups and time intervals analysed. BDG testing was less specific (90-93\%) than GM testing (99-100\%). Combining BDG and GM testing resulted in sensitivity/specificity of 70\%/91\%. Often, BDG testing was positive before GM testing. Our study backs the use of BDG for diagnosis of suspected IA. We suggest combining BDG and GM to improve the overall sensitivity.},
  language  = {en}
}
@article{SuratVogelWiegeringetal.2021,
  author    = {Surat, G{\"u}zin and Vogel, Ulrich and Wiegering, Armin and Germer, Christoph-Thomas and Lock, Johan Friso},
  title     = {Defining the scope of antimicrobial stewardship interventions on the prescription quality of antibiotics for surgical intra-abdominal infections},
  series = {Antibiotics},
  volume    = {10},
  journal   = {Antibiotics},
  number    = {1},
  issn      = {2079-6382},
  doi       = {10.3390/antibiotics10010073},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-223034},
  year      = {2021},
  abstract  = {Background: The aim of this study was to assess the impact of antimicrobial stewardship interventions on surgical antibiotic prescription behavior in the management of non-elective surgical intra-abdominal infections, focusing on postoperative antibiotic use, including the appropriateness of indications. Methods: A single-center quality improvement study with retrospective evaluation of the impact of antimicrobial stewardship measures on optimizing antibacterial use in intra-abdominal infections requiring emergency surgery was performed. The study was conducted in a tertiary hospital in Germany from January 1, 2016, to January 30, 2020, three years after putting a set of antimicrobial stewardship standards into effect. Results: 767 patients were analyzed (n = 495 in 2016 and 2017, the baseline period; n = 272 in 2018, the antimicrobial stewardship period). The total days of therapy per 100 patient days declined from 47.0 to 42.2 days (p = 0.035). The rate of patients receiving postoperative therapy decreased from 56.8\% to 45.2\% (p = 0.002), comparing both periods. There was a significant decline in the rate of inappropriate indications (17.4\% to 8.1 \%, p = 0.015) as well as a significant change from broad-spectrum to narrow-spectrum antibiotic use (28.8\% to 6.5\%, p ≤ 0.001) for postoperative therapy. The significant decline in antibiotic use did not affect either clinical outcomes or the rate of postoperative wound complications. Conclusions: Postoperative antibiotic use for intra-abdominal infections could be significantly reduced by antimicrobial stewardship interventions. The identification of inappropriate indications remains a key target for antimicrobial stewardship programs.},
  language  = {en}
}
@phdthesis{Muenstermann2022,
  author    = {M{\"u}nstermann, Marcel},
  title     = {The roles of the anaphylatoxin receptors during invasive disease as well as mucosal colonization caused by \(Neisseria\) \(meningitidis\)},
  doi       = {10.25972/OPUS-26975},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-269759},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2022},
  abstract  = {The human specific gram-negative bacterium Neisseria meningitidis (Nme, meningococci) is a common colonizer of the upper respiratory tract. Upon becoming invasive, Nme can cause meningitis and life-threatening sepsis. The most important immune defense mechanism in invasive meningococcal disease (IMD) is the complement mediated killing of bacteria. The complement cascade is activated through different pathogen associated patterns and finally leads to the lysis of the bacteria by the membrane attack complex. In addition to the direct bacterial killing, the complement system is also an important player in different inflammatory processes. A hallmark of IMD is an overreaction of the immune system and the release of the potent anaphylatoxins C3a and C5a by the complement system is an important factor hereby. There are three anaphylatoxin receptors (ATRs), the C3aR, the C5aR1 and the C5aR2, capable of detecting these anaphylatoxins. It has already been shown that blocking the ATR C5aR1 strongly benefitted the outcome of IMD in a murine sepsis model. However, the roles of ATRs C3aR and C5aR2 in IMD are still unclear. This work aims to analyze the role of these ATRs in meningococcal sepsis and to identify possible underlying mechanisms. Furthermore, a possible involvement of the complement system, the ATRs and the type II CRISPR/Cas system on nasopharyngeal colonization is analyzed. In vivo depletion experiments showed that without neutrophils or monocytes/macrophages the complement system alone was not able to clear a low dose Nme infection, which highlights the importance of cellular components in IMD. Analyzing the role of the ATRs in knock-out mice with high dose Nme infections, revealed that the lack of C5aR2, like the lack of C5aR1, was beneficial for the outcome of meningococcal induced sepsis. In contrast, the lack of C3aR in knock-out mice was detrimental. The positive outcome associated with the C5aRs could be reproduced by using an antagonist against both C5aRs or an antagonist specifically against C5aR1 in WT mice. These findings are giving hope to future therapeutic applications. Next, a possible contribution of neutrophils to this positive outcome was analyzed. Absence of C5aR1 led to a decrease of degranulation by neutrophils in a murine whole blood model, while the other ATRs showed no effect. Neutrophil analysis in human whole blood, on the other hand, revealed a reduced oxidative burst and IL-8 secretion upon inhibition of all three ATRs. A functional difference between the C5aRs and the C3aR in neutrophils was observed in phagocytosis, which was reduced upon C3aR inhibition, but was unaltered with C5aR1 or C5aR2 inhibition. Possible underlying mechanisms in the phosphorylation of ERK1/2 were analyzed in bone marrow derived macrophages isolated from ATR knock-out mice. The later phosphorylation of ERK1/2 in macrophages without C5aR1 or C5aR2 expression might explain, why blocking the C5aRs is beneficial for the outcome of IMD in mice. In contrast to these findings, the colonization of the nasopharynx in huCEACAM 1 expressing mice by Nme did not seem to depend on the Complement system factors C3 and C5 nor the ATRs. Additionally, no difference in the colonization could be observed in this model using Nme mutants lacking different parts of the type 2 CRISPR/Cas system. Conclusively, this work highlights the importance of the complement system, the ATRs and the cellular components in IMD. Contrariwise, these factors did not play a role in the analyzed nasopharyngeal infection model. The beneficial effects of C5aR1 and C5aR2 lack/inhibition in IMD might have medicinal applications, which could support the standard therapies of IMD in the future.},
  subject      = {Anaphylatoxine},
  language  = {en}
}
@article{WaltherWagnerKurzai2019,
  author    = {Walther, Grit and Wagner, Lysett and Kurzai, Oliver},
  title     = {Updates on the taxonomy of Mucorales with an emphasis on clinically important taxa},
  series = {Journal of Fungi},
  volume    = {5},
  journal   = {Journal of Fungi},
  number    = {4},
  issn      = {2309-608X},
  doi       = {10.3390/jof5040106},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-193081},
  year      = {2019},
  abstract  = {Fungi of the order Mucorales colonize all kinds of wet, organic materials and represent a permanent part of the human environment. They are economically important as fermenting agents of soybean products and producers of enzymes, but also as plant parasites and spoilage organisms. Several taxa cause life-threatening infections, predominantly in patients with impaired immunity. The order Mucorales has now been assigned to the phylum Mucoromycota and is comprised of 261 species in 55 genera. Of these accepted species, 38 have been reported to cause infections in humans, as a clinical entity known as mucormycosis. Due to molecular phylogenetic studies, the taxonomy of the order has changed widely during the last years. Characteristics such as homothallism, the shape of the suspensors, or the formation of sporangiola are shown to be not taxonomically relevant. Several genera including Absidia, Backusella, Circinella, Mucor, and Rhizomucor have been amended and their revisions are summarized in this review. Medically important species that have been affected by recent changes include Lichtheimia corymbifera, Mucor circinelloides, and Rhizopus microsporus. The species concept of Rhizopus arrhizus (syn. R. oryzae) is still a matter of debate. Currently, species identification of the Mucorales is best performed by sequencing of the internal transcribed spacer (ITS) region. Ecologically, the Mucorales represent a diverse group but for the majority of taxa, the ecological role and the geographic distribution remain unknown. Understanding the biology of these opportunistic fungal pathogens is a prerequisite for the prevention of infections, and, consequently, studies on the ecology of the Mucorales are urgently needed.},
  language  = {en}
}
@article{MottolaRamirezZavalaHuenningeretal.2021,
  author    = {Mottola, Austin and Ram{\´i}rez-Zavala, Bernardo and H{\"u}nninger, Kerstin and Kurzai, Oliver and Morschh{\"a}user, Joachim},
  title     = {The zinc cluster transcription factor Czf1 regulates cell wall architecture and integrity in Candida albicans},
  series = {Molecular Microbiology},
  volume    = {116},
  journal   = {Molecular Microbiology},
  number    = {2},
  doi       = {10.1111/mmi.14727},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-259583},
  pages     = {483-497},
  year      = {2021},
  abstract  = {The fungal cell wall is essential for the maintenance of cellular integrity and mediates interactions of the cells with the environment. It is a highly flexible organelle whose composition and organization is modulated in response to changing growth conditions. In the pathogenic yeast Candida albicans, a network of signaling pathways regulates the structure of the cell wall, and mutants with defects in these pathways are hypersensitive to cell wall stress. By harnessing a library of genetically activated forms of all C. albicans zinc cluster transcription factors, we found that a hyperactive Czf1 rescued the hypersensitivity to cell wall stress of different protein kinase deletion mutants. The hyperactive Czf1 induced the expression of many genes with cell wall-related functions and caused visible changes in the cell wall structure. C. albicans czf1Δ mutants were hypersensitive to the antifungal drug caspofungin, which inhibits cell wall biosynthesis. The changes in cell wall architecture caused by hyperactivity or absence of Czf1 resulted in an increased recognition of C. albicans by human neutrophils. Our results show that Czf1, which is known as a regulator of filamentous growth and white-opaque switching, controls the expression of cell wall genes and modulates the architecture of the cell wall.},
  language  = {en}
}
@article{PetersKaiserFinketal.2021,
  author    = {Peters, Simon and Kaiser, Lena and Fink, Julian and Schumacher, Fabian and Perschin, Veronika and Schlegel, Jan and Sauer, Markus and Stigloher, Christian and Kleuser, Burkhard and Seibel, Juergen and Schubert-Unkmeir, Alexandra},
  title     = {Click-correlative light and electron microscopy (click-AT-CLEM) for imaging and tracking azido-functionalized sphingolipids in bacteria},
  series = {Scientific Reports},
  volume    = {11},
  journal   = {Scientific Reports},
  number    = {1},
  doi       = {10.1038/s41598-021-83813-w},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-259147},
  pages     = {4300},
  year      = {2021},
  abstract  = {Sphingolipids, including ceramides, are a diverse group of structurally related lipids composed of a sphingoid base backbone coupled to a fatty acid side chain and modified terminal hydroxyl group. Recently, it has been shown that sphingolipids show antimicrobial activity against a broad range of pathogenic microorganisms. The antimicrobial mechanism, however, remains so far elusive. Here, we introduce 'click-AT-CLEM', a labeling technique for correlated light and electron microscopy (CLEM) based on the super-resolution array tomography (srAT) approach and bio-orthogonal click chemistry for imaging of azido-tagged sphingolipids to directly visualize their interaction with the model Gram-negative bacterium Neisseria meningitidis at subcellular level. We observed ultrastructural damage of bacteria and disruption of the bacterial outer membrane induced by two azido-modified sphingolipids by scanning electron microscopy and transmission electron microscopy. Click-AT-CLEM imaging and mass spectrometry clearly revealed efficient incorporation of azido-tagged sphingolipids into the outer membrane of Gram-negative bacteria as underlying cause of their antimicrobial activity.},
  language  = {en}
}
@article{MarincolaLiongSchoenetal.2021,
  author    = {Marincola, Gabriella and Liong, Olivia and Schoen, Christoph and Abouelfetouh, Alaa and Hamdy, Aisha and Wencker, Freya D. R. and Marciniak, Tessa and Becker, Karsten and K{\"o}ck, Robin and Ziebuhr, Wilma},
  title     = {Antimicrobial Resistance Profiles of Coagulase-Negative Staphylococci in Community-Based Healthy Individuals in Germany},
  series = {Frontiers in Public Health},
  volume    = {9},
  journal   = {Frontiers in Public Health},
  issn      = {2296-2565},
  doi       = {10.3389/fpubh.2021.684456},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-240881},
  year      = {2021},
  abstract  = {Coagulase-negative staphylococci (CoNS) are common opportunistic pathogens, but also ubiquitous human and animal commensals. Infection-associated CoNS from healthcare environments are typically characterized by pronounced antimicrobial resistance (AMR) including both methicillin- and multidrug-resistant isolates. Less is known about AMR patterns of CoNS colonizing the general population. Here we report on AMR in commensal CoNS recovered from 117 non-hospitalized volunteers in a region of Germany with a high livestock density. Among the 69 individuals colonized with CoNS, 29 had reported contacts to either companion or farm animals. CoNS were selectively cultivated from nasal swabs, followed by species definition by 16S rDNA sequencing and routine antibiotic susceptibility testing. Isolates displaying phenotypic AMR were further tested by PCR for presence of selected AMR genes. A total of 127 CoNS were isolated and Staphylococcus epidermidis (75\%) was the most common CoNS species identified. Nine isolates (7\%) were methicillin-resistant (MR) and carried the mecA gene, with seven individuals (10\%) being colonized with at least one MR-CoNS isolate. While resistance against gentamicin, phenicols and spectinomycin was rare, high resistance rates were found against tetracycline (39\%), erythromycin (33\%) and fusidic acid (24\%). In the majority of isolates, phenotypic resistance could be associated with corresponding AMR gene detection. Multidrug-resistance (MDR) was observed in 23\% (29/127) of the isolates, with 33\% (23/69) of the individuals being colonized with MDR-CoNS. The combined data suggest that MR- and MDR-CoNS are present in the community, with previous animal contact not significantly influencing the risk of becoming colonized with such isolates.},
  language  = {en}
}
@article{PageWallstabeLotheretal.2021,
  author    = {Page, Lukas and Wallstabe, Julia and Lother, Jasmin and Bauser, Maximilian and Kniemeyer, Olaf and Strobel, Lea and Voltersen, Vera and Teutschbein, Janka and Hortschansky, Peter and Morton, Charles Oliver and Brakhage, Axel A. and Topp, Max and Einsele, Hermann and Wurster, Sebastian and Loeffler, Juergen},
  title     = {CcpA- and Shm2-Pulsed Myeloid Dendritic Cells Induce T-Cell Activation and Enhance the Neutrophilic Oxidative Burst Response to Aspergillus fumigatus},
  series = {Frontiers in Immunology},
  volume    = {12},
  journal   = {Frontiers in Immunology},
  issn      = {1664-3224},
  doi       = {10.3389/fimmu.2021.659752},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-239493},
  year      = {2021},
  abstract  = {Aspergillus fumigatus causes life-threatening opportunistic infections in immunocompromised patients. As therapeutic outcomes of invasive aspergillosis (IA) are often unsatisfactory, the development of targeted immunotherapy remains an important goal. Linking the innate and adaptive immune system, dendritic cells are pivotal in anti-Aspergillus defense and have generated interest as a potential immunotherapeutic approach in IA. While monocyte-derived dendritic cells (moDCs) require ex vivo differentiation, antigen-pulsed primary myeloid dendritic cells (mDCs) may present a more immediate platform for immunotherapy. To that end, we compared the response patterns and cellular interactions of human primary mDCs and moDCs pulsed with an A. fumigatus lysate and two A. fumigatus proteins (CcpA and Shm2) in a serum-free, GMP-compliant medium. CcpA and Shm2 triggered significant upregulation of maturation markers in mDCs and, to a lesser extent, moDCs. Furthermore, both A. fumigatus proteins elicited the release of an array of key pro-inflammatory cytokines including TNF-α, IL-1β, IL-6, IL-8, and CCL3 from both DC populations. Compared to moDCs, CcpA- and Shm2-pulsed mDCs exhibited greater expression of MHC class II antigens and stimulated stronger proliferation and IFN-γ secretion from autologous CD4\(^+\) and CD8\(^+\) T-cells. Moreover, supernatants of CcpA- and Shm2-pulsed mDCs significantly enhanced the oxidative burst in allogeneic neutrophils co-cultured with A. fumigatus germ tubes. Taken together, our in vitro data suggest that ex vivo CcpA- and Shm2-pulsed primary mDCs have the potential to be developed into an immunotherapeutic approach to tackle IA.},
  language  = {en}
}
@article{MachataSreekantapuramHuennigeretal.2021,
  author    = {Machata, Silke and Sreekantapuram, Sravya and H{\"u}nniger, Kerstin and Kurzai, Oliver and Dunker, Christine and Schubert, Katja and Kr{\"u}ger, Wibke and Schulze-Richter, Bianca and Speth, Cornelia and Rambach, G{\"u}nter and Jacobsen, Ilse D.},
  title     = {Significant Differences in Host-Pathogen Interactions Between Murine and Human Whole Blood},
  series = {Frontiers in Immunology},
  volume    = {11},
  journal   = {Frontiers in Immunology},
  issn      = {1664-3224},
  doi       = {10.3389/fimmu.2020.565869},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-222575},
  year      = {2021},
  abstract  = {Murine infection models are widely used to study systemic candidiasis caused by C. albicans. Whole-blood models can help to elucidate host-pathogens interactions and have been used for several Candida species in human blood. We adapted the human whole-blood model to murine blood. Unlike human blood, murine blood was unable to reduce fungal burden and more substantial filamentation of C. albicans was observed. This coincided with less fungal association with leukocytes, especially neutrophils. The lower neutrophil number in murine blood only partially explains insufficient infection and filamentation control, as spiking with murine neutrophils had only limited effects on fungal killing. Furthermore, increased fungal survival is not mediated by enhanced filamentation, as a filament-deficient mutant was likewise not eliminated. We also observed host-dependent differences for interaction of platelets with C. albicans, showing enhanced platelet aggregation, adhesion and activation in murine blood. For human blood, opsonization was shown to decrease platelet interaction suggesting that complement factors interfere with fungus-to-platelet binding. Our results reveal substantial differences between murine and human whole-blood models infected with C. albicans and thereby demonstrate limitations in the translatability of this ex vivo model between hosts.},
  language  = {en}
}
@article{PetersFohmannRudeletal.2021,
  author    = {Peters, Simon and Fohmann, Ingo and Rudel, Thomas and Schubert-Unkmeir, Alexandra},
  title     = {A Comprehensive Review on the Interplay between Neisseria spp. and Host Sphingolipid Metabolites},
  series = {Cells},
  volume    = {10},
  journal   = {Cells},
  number    = {11},
  issn      = {2073-4409},
  doi       = {10.3390/cells10113201},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-250203},
  year      = {2021},
  abstract  = {Sphingolipids represent a class of structural related lipids involved in membrane biology and various cellular processes including cell growth, apoptosis, inflammation and migration. Over the past decade, sphingolipids have become the focus of intensive studies regarding their involvement in infectious diseases. Pathogens can manipulate the sphingolipid metabolism resulting in cell membrane reorganization and receptor recruitment to facilitate their entry. They may recruit specific host sphingolipid metabolites to establish a favorable niche for intracellular survival and proliferation. In contrast, some sphingolipid metabolites can also act as a first line defense against bacteria based on their antimicrobial activity. In this review, we will focus on the strategies employed by pathogenic Neisseria spp. to modulate the sphingolipid metabolism and hijack the sphingolipid balance in the host to promote cellular colonization, invasion and intracellular survival. Novel techniques and innovative approaches will be highlighted that allow imaging of sphingolipid derivatives in the host cell as well as in the pathogen.},
  language  = {en}
}
@article{BeierleSchobelVogeletal.2021,
  author    = {Beierle, Felix and Schobel, Johannes and Vogel, Carsten and Allgaier, Johannes and Mulansky, Lena and Haug, Fabian and Haug, Julian and Schlee, Winfried and Holfelder, Marc and Stach, Michael and Schickler, Marc and Baumeister, Harald and Cohrdes, Caroline and Deckert, J{\"u}rgen and Deserno, Lorenz and Edler, Johanna-Sophie and Eichner, Felizitas A. and Greger, Helmut and Hein, Grit and Heuschmann, Peter and John, Dennis and Kestler, Hans A. and Krefting, Dagmar and Langguth, Berthold and Meybohm, Patrick and Probst, Thomas and Reichert, Manfred and Romanos, Marcel and St{\"o}rk, Stefan and Terhorst, Yannik and Weiß, Martin and Pryss, R{\"u}diger},
  title     = {Corona Health — A Study- and Sensor-Based Mobile App Platform Exploring Aspects of the COVID-19 Pandemic},
  series = {International Journal of Environmental Research and Public Health},
  volume    = {18},
  journal   = {International Journal of Environmental Research and Public Health},
  number    = {14},
  issn      = {1660-4601},
  doi       = {10.3390/ijerph18147395},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-242658},
  year      = {2021},
  abstract  = {Physical and mental well-being during the COVID-19 pandemic is typically assessed via surveys, which might make it difficult to conduct longitudinal studies and might lead to data suffering from recall bias. Ecological momentary assessment (EMA) driven smartphone apps can help alleviate such issues, allowing for in situ recordings. Implementing such an app is not trivial, necessitates strict regulatory and legal requirements, and requires short development cycles to appropriately react to abrupt changes in the pandemic. Based on an existing app framework, we developed Corona Health, an app that serves as a platform for deploying questionnaire-based studies in combination with recordings of mobile sensors. In this paper, we present the technical details of Corona Health and provide first insights into the collected data. Through collaborative efforts from experts from public health, medicine, psychology, and computer science, we released Corona Health publicly on Google Play and the Apple App Store (in July 2020) in eight languages and attracted 7290 installations so far. Currently, five studies related to physical and mental well-being are deployed and 17,241 questionnaires have been filled out. Corona Health proves to be a viable tool for conducting research related to the COVID-19 pandemic and can serve as a blueprint for future EMA-based studies. The data we collected will substantially improve our knowledge on mental and physical health states, traits and trajectories as well as its risk and protective factors over the course of the COVID-19 pandemic and its diverse prevention measures.},
  language  = {en}
}
@article{KruegerLeskienSchulleretal.2021,
  author    = {Kr{\"u}ger, S{\"o}ren and Leskien, Miriam and Schuller, Patricia and Prifert, Christiane and Weißbrich, Benedikt and Vogel, Ulrich and Krone, Manuel},
  title     = {Performance and feasibility of universal PCR admission screening for SARS-CoV-2 in a German tertiary care hospital},
  series = {Journal of Medical Virology},
  volume    = {93},
  journal   = {Journal of Medical Virology},
  number    = {5},
  doi       = {10.1002/jmv.26770},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-238971},
  pages     = {2890 -- 2898},
  year      = {2021},
  abstract  = {Anamnestic screening of symptoms and contact history is applied to identify coronavirus disease 2019 (COVID-19) patients on admission. However, asymptomatic and presymptomatic patients remain undetected although the viral load may be high. In this retrospective cohort study, all hospitalized patients who received polymerase chain reaction (PCR) admission testing from March 26th until May 24th, 2020 were included. Data on COVID-19-specific symptoms and contact history to COVID-19 cases were retrospectively extracted from patient files and from contact tracing notes. The compliance to the universal testing protocol was high with 90\%. Out of 6940 tested patients, 27 new severe acute respiratory syndrome coronavirus-2 infections (0.4\%) were detected. Seven of those COVID-19 cases (26\% of all new cases) were asymptomatic and had no positive contact history, but were identified through a positive PCR test. The number needed to identify an asymptomatic patient was 425 in the first wave of the epidemic, 1218 in the low incidence phase. The specificity of the method was above 99.9\%. Universal PCR testing was highly accepted by staff as demonstrated by high compliance. The costs to detect one asymptomatic case in future studies need to be traded off against the costs and damage caused by potential outbreaks of COVID-19.},
  language  = {en}
}