@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{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{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{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} } @phdthesis{Schlag2017, author = {Schlag, Stephanie}, title = {Mikrobiologie, Klinik und Antibiotika-Therapie invasiver bakterieller Infektionen an der W{\"u}rzburger Universit{\"a}ts-Kinderklinik zwischen 2006 und 2012}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-156236}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2017}, abstract = {In einem Zeitraum von sieben Jahren untersuchten wir invasive bakterielle Infektionen bei Kindern durch die wichtigsten Erreger von Blutstrombahninfektionen an der W{\"u}rzburger Universit{\"a}ts-Kinderklinik.}, subject = {Antibiotikum}, language = {de} } @article{StockPetrašMelteretal.2016, author = {Stock, Nina Katharina and Petr{\´a}š, Petr and Melter, Oto and Kapounov{\´a}, Gabriela and Vopalkov{\´a}, Petra and Kubele, Jan and Vaniš, V{\´a}clav and Tkadlec, Jan and Buk{\´a}čkov{\´a}, Eva and Machov{\´a}, Ivana and Jindr{\´a}k, Vlastimil}, title = {Importance of Multifaceted Approaches in Infection Control: A Practical Experience from an Outbreak Investigation}, series = {PLoS ONE}, volume = {11}, journal = {PLoS ONE}, number = {6}, doi = {10.1371/journal.pone.0157981}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-166891}, pages = {e0157981}, year = {2016}, abstract = {Background This study presents the results of a multidisciplinary, nosocomial MRSA outbreak investigation in an 8-bed medical intensive care unit (ICU). The identification of seven MRSA positive patients in the beginning of 2014 led to the closure of the ward for several weeks. A multidisciplinary, retrospective investigation was initiated in order to identify the reason and the source for the outbreak, describe MRSA transmission in the department and identify limitations in infection control. Methods The investigation comprised an epidemiological description of MRSA cases from 2012 to 2014 and a characterization of MRSA isolates, including phage-, spa- and PFGE-typing. Additionally, MRSA screening was performed from the hospital staff and the environment. To identify the reason for the outbreak, work-related, psychological and behavioral factors were investigated by impartial audits and staff interviews. Results Thirty-one MRSA cases were registered during the study period, and 36 isolates were investigated. Molecular typing determined the outbreak strain (phage type 54/812, PFGE type A4, spa type t003) and identified the probable index case. Nasal carriage in one employee and a high environmental contamination with the outbreak strain was documented. Important gaps in nursing procedures and general management were identified. Elevated stress levels and communication problems preceded the outbreak. Compliance with hand hygiene and isolation procedures was evaluated as appropriate. Conclusion This study demonstrates the complexity of controlling hospital-associated infections. The combined use of different typing methods is beneficial for outbreak investigations. Psychological, behavioral and other work-related factors have an important impact on the spread of nosocomial pathogens. These factors should be addressed and integrated in routine infection control practice.}, 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{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{KochHellenbrandSchinketal.2016, author = {Koch, J. and Hellenbrand, W. and Schink, S. and Wichmann, O. and Carganico, A. and Drewes, J. and Kruspe, M. and Suckau, M. and Claus, H. and Marcus, U.}, title = {Evaluation of a temporary vaccination recommendation in response to an outbreak of invasive meningococcal serogroup C disease in men who have sex with men in Berlin, 2013-2014}, series = {Eurosurveillance}, volume = {21}, journal = {Eurosurveillance}, number = {5}, doi = {10.2807/1560-7917.ES.2016.21.5.30122}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-165070}, pages = {pii=30122}, year = {2016}, abstract = {Meningococcal serogroup C (MenC) vaccination of men who have sex with men (MSM) was temporarily recommended to control an outbreak of invasive MenC disease among MSM in Berlin in 2012-2013. Vaccination was offered to HIV-infected MSM free of charge; others had to request reimbursement or pay out of pocket. We aimed to assess (i) awareness and acceptance of this recommendation through an online survey of MSM, (ii) implementation through a survey of primary care physicians and analysis of vaccine prescriptions, and (iii) impact through analysis of notified cases. Among online survey respondents, 60\% were aware of the recommendation. Of these, 39\% had obtained vaccination (70\% of HIV-infected, 13\% of HIV-negative/non-tested MSM). Awareness of recommendation and vaccination were positively associated with HIV infection, primary care physicians' awareness of respondents' sexual orientation, and exposure to multiple information sources. Most (26/30) physicians informed clients about the recommendation. Physicians considered concerns regarding reimbursement, vaccine safety and lack of perceived disease risk as primary barriers. After the recommendation, no further outbreak-related cases occurred. To reach and motivate target groups, communication of a new outbreak-related vaccination recommendation should address potential concerns through as many information channels as possible and direct reimbursement of costs should be enabled.}, language = {en} } @article{WeissSchlegelTerpitzetal.2020, author = {Weiss, Esther and Schlegel, Jan and Terpitz, Ulrich and Weber, Michael and Linde, J{\"o}rg and Schmitt, Anna-Lena and H{\"u}nniger, Kerstin and Marischen, Lothar and Gamon, Florian and Bauer, Joachim and L{\"o}ffler, Claudia and Kurzai, Oliver and Morton, Charles Oliver and Sauer, Markus and Einsele, Hermann and Loeffler, Juergen}, title = {Reconstituting NK Cells After Allogeneic Stem Cell Transplantation Show Impaired Response to the Fungal Pathogen Aspergillus fumigatus}, series = {Frontiers in Immunology}, volume = {11}, journal = {Frontiers in Immunology}, issn = {1664-3224}, doi = {10.3389/fimmu.2020.02117}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-212581}, year = {2020}, abstract = {Delayed natural killer (NK) cell reconstitution after allogeneic stem cell transplantation (alloSCT) is associated with a higher risk of developing invasive aspergillosis. The interaction of NK cells with the human pathogen Aspergillus (A.) fumigatus is mediated by the fungal recognition receptor CD56, which is relocated to the fungal interface after contact. Blocking of CD56 signaling inhibits the fungal mediated chemokine secretion of MIP-1α, MIP-1β, and RANTES and reduces cell activation, indicating a functional role of CD56 in fungal recognition. We collected peripheral blood from recipients of an allograft at defined time points after alloSCT (day 60, 90, 120, 180). NK cells were isolated, directly challenged with live A. fumigatus germ tubes, and cell function was analyzed and compared to healthy age and gender-matched individuals. After alloSCT, NK cells displayed a higher percentage of CD56\(^{bright}\)CD16\(^{dim}\) cells throughout the time of blood collection. However, CD56 binding and relocalization to the fungal contact side were decreased. We were able to correlate this deficiency to the administration of corticosteroid therapy that further negatively influenced the secretion of MIP-1α, MIP-1β, and RANTES. As a consequence, the treatment of healthy NK cells ex vivo with corticosteroids abrogated chemokine secretion measured by multiplex immunoassay. Furthermore, we analyzed NK cells regarding their actin cytoskeleton by Structured Illumination Microscopy (SIM) and flow cytometry and demonstrate an actin dysfunction of NK cells shown by reduced F-actin content after fungal co-cultivation early after alloSCT. This dysfunction remains until 180 days post-alloSCT, concluding that further actin-dependent cellular processes may be negatively influenced after alloSCT. To investigate the molecular pathomechansism, we compared CD56 receptor mobility on the plasma membrane of healthy and alloSCT primary NK cells by single-molecule tracking. The results were very robust and reproducible between tested conditions which point to a different molecular mechanism and emphasize the importance of proper CD56 mobility.}, 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{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{SilwedelHaarmannFehrholzetal.2019, author = {Silwedel, Christine and Haarmann, Axel and Fehrholz, Markus and Claus, Heike and Speer, Christian P. and Glaser, Kirsten}, title = {More than just inflammation: Ureaplasma species induce apoptosis in human brain microvascular endothelial cells}, series = {Journal of Neuroinflammation}, volume = {16}, journal = {Journal of Neuroinflammation}, doi = {10.1186/s12974-019-1413-8}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-200711}, pages = {38}, year = {2019}, abstract = {Background Ureaplasma species (spp.) are commonly regarded as low-virulent commensals but may cause invasive diseases in immunocompromised adults and in neonates, including neonatal meningitis. The interactions of Ureaplasma spp. with host defense mechanisms are poorly understood. This study addressed Ureaplasma-driven cell death, concentrating on apoptosis as well as inflammatory cell death. Methods Human brain microvascular endothelial cells (HBMEC) were exposed to Ureaplasma (U.) urealyticum serovar 8 (Uu8) and U. parvum serovar 3 (Up3). Resulting numbers of dead cells as well as mRNA levels and enzyme activity of key agents in programmed cell death were assessed by flow cytometry, RNA sequencing, and qRT-PCR, respectively. xCELLigence data were used for real-time monitoring of changes in cell adhesion properties. Results Both Ureaplasma isolates induced cell death (p < 0.05, vs. broth). Furthermore, Ureaplasma spp. enhanced mRNA levels for genes in apoptosis, including caspase 3 (Up3 p < 0.05, vs. broth), caspase 7 (p < 0.01), and caspase 9 (Up3 p < 0.01). Caspase 3 activity was increased upon Uu8 exposure (p < 0.01). Vice versa, Ureaplasma isolates downregulated mRNA levels for proteins involved in inflammatory cell death, namely caspase 1 (Uu8 p < 0.01, Up3 p < 0.001), caspase 4 (Uu8 p < 0.05, Up3 p < 0.01), NOD-like receptor pyrin domain-containing 3 (Uu8 p < 0.05), and receptor-interacting protein kinase 3 (p < 0.05). Conclusions By inducing apoptosis in HBMEC as main constituents of the blood-brain barrier, Ureaplasma spp. may provoke barrier breakdown. Simultaneous suppression of inflammatory cell death may additionally attenuate host defense strategies. Ultimate consequence could be invasive and long-term CNS infections by Ureaplasma spp.}, 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{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{AmpattuHagmannLiangetal.2017, author = {Ampattu, Biju Joseph and Hagmann, Laura and Liang, Chunguang and Dittrich, Marcus and Schl{\"u}ter, Andreas and Blom, Jochen and Krol, Elizaveta and Goesmann, Alexander and Becker, Anke and Dandekar, Thomas and M{\"u}ller, Tobias and Schoen, Christoph}, title = {Transcriptomic buffering of cryptic genetic variation contributes to meningococcal virulence}, series = {BMC Genomics}, volume = {18}, journal = {BMC Genomics}, number = {282}, doi = {10.1186/s12864-017-3616-7}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-157534}, year = {2017}, abstract = {Background: Commensal bacteria like Neisseria meningitidis sometimes cause serious disease. However, genomic comparison of hyperinvasive and apathogenic lineages did not reveal unambiguous hints towards indispensable virulence factors. Here, in a systems biological approach we compared gene expression of the invasive strain MC58 and the carriage strain α522 under different ex vivo conditions mimicking commensal and virulence compartments to assess the strain-specific impact of gene regulation on meningococcal virulence. Results: Despite indistinguishable ex vivo phenotypes, both strains differed in the expression of over 500 genes under infection mimicking conditions. These differences comprised in particular metabolic and information processing genes as well as genes known to be involved in host-damage such as the nitrite reductase and numerous LOS biosynthesis genes. A model based analysis of the transcriptomic differences in human blood suggested ensuing metabolic flux differences in energy, glutamine and cysteine metabolic pathways along with differences in the activation of the stringent response in both strains. In support of the computational findings, experimental analyses revealed differences in cysteine and glutamine auxotrophy in both strains as well as a strain and condition dependent essentiality of the (p)ppGpp synthetase gene relA and of a short non-coding AT-rich repeat element in its promoter region. Conclusions: Our data suggest that meningococcal virulence is linked to transcriptional buffering of cryptic genetic variation in metabolic genes including global stress responses. They further highlight the role of regulatory elements for bacterial virulence and the limitations of model strain approaches when studying such genetically diverse species as N. meningitidis.}, language = {en} } @article{KlughammerDittrichBlometal.2017, author = {Klughammer, Johanna and Dittrich, Marcus and Blom, Jochen and Mitesser, Vera and Vogel, Ulrich and Frosch, Matthias and Goesmann, Alexander and M{\"u}ller, Tobias and Schoen, Christoph}, title = {Comparative genome sequencing reveals within-host genetic changes in Neisseria meningitidis during invasive disease}, series = {PLoS ONE}, volume = {12}, journal = {PLoS ONE}, number = {1}, doi = {10.1371/journal.pone.0169892}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-159547}, pages = {e0169892}, year = {2017}, abstract = {Some members of the physiological human microbiome occasionally cause life-threatening disease even in immunocompetent individuals. A prime example of such a commensal pathogen is Neisseria meningitidis, which normally resides in the human nasopharynx but is also a leading cause of sepsis and epidemic meningitis. Using N. meningitidis as model organism, we tested the hypothesis that virulence of commensal pathogens is a consequence of within host evolution and selection of invasive variants due to mutations at contingency genes, a mechanism called phase variation. In line with the hypothesis that phase variation evolved as an adaptation to colonize diverse hosts, computational comparisons of all 27 to date completely sequenced and annotated meningococcal genomes retrieved from public databases showed that contingency genes are indeed enriched for genes involved in host interactions. To assess within-host genetic changes in meningococci, we further used ultra-deep whole-genome sequencing of throat-blood strain pairs isolated from four patients suffering from invasive meningococcal disease. We detected up to three mutations per strain pair, affecting predominantly contingency genes involved in type IV pilus biogenesis. However, there was not a single (set) of mutation(s) that could invariably be found in all four pairs of strains. Phenotypic assays further showed that these genetic changes were generally not associated with increased serum resistance, higher fitness in human blood ex vivo or differences in the interaction with human epithelial and endothelial cells in vitro. In conclusion, we hypothesize that virulence of meningococci results from accidental emergence of invasive variants during carriage and without within host evolution of invasive phenotypes during disease progression in vivo.}, 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{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} } @phdthesis{vonPapen2019, author = {von Papen, Hans Michael}, title = {Untersuchungen zum Einfluss der Meningokokkeninfektion auf den Zellzyklus von Epithelzellen}, doi = {10.25972/OPUS-19286}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-192862}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2019}, abstract = {Zahlreiche humanpathogene bakterielle Erreger k{\"o}nnen ihre F{\"a}higkeit zur Kolonisation epithelialer Barrieren optimieren, indem sie mit dem Zellzyklus der infizierten Wirtszelle in Wechselwirkung treten und so die Abschilferung und Erneuerung des Epithels verz{\"o}gern. Die hierbei wirksamen bakteriellen Effektoren sind als „Cyclomoduline" bekannt und gelten als neue Klasse bakterieller Pathogenit{\"a}tsfaktoren. Ziel der vorliegenden Promotionsarbeit war es zu untersuchen, ob durch die Infektion menschlicher pharyngealer Epithelzellen mit N. meningitidis der Zellzyklus der Wirtszelle beeinflusst wird. Mit zwei verschiedenen Untersuchungsmethoden konnte {\"u}bereinstimmend gezeigt werden, dass die Infektion der Epithelzelllinie Detroit 562 mit verschiedenen Meningokokkenisolaten zu einer signifikanten Akkumulation von Epithelzellen in der G1-Phase f{\"u}hrte. Dieser Effekt wurde sowohl von pathogenen Meningokokkenst{\"a}mmen als auch von Tr{\"a}gerst{\"a}mmen ausgel{\"o}st, jedoch nur durch Isolate, die f{\"a}hig zur Adh{\"a}renz und zur Invasion in die Epithelzelle waren. Durch Hitzebehandlung der Bakterien konnte der Zellzyklusarrest vollst{\"a}ndig aufgehoben werden. Ebenso konnte der Effekt durch Inkubation der Epithelzellen mit bakteriellen Kultur{\"u}berst{\"a}nden und durch Infektion der Zellen mit E. coli-St{\"a}mmen, welche die Meningokokkenadh{\"a}sine Opa und Opc {\"u}berexprimieren, nicht ausgel{\"o}st werden. Es konnte weiterhin nachgewiesen werden, dass die Infektion mit N. meningitidis in der Zielzelle zu einer signifikant gesteigerten Expression des CDK-Inhibitors p21WAF1/Cip1 f{\"u}hrte, begleitet von einer vermehrten Lokalisation im Zellkern. Auch zeigte sich eine ver{\"a}nderte Proteinexpression der f{\"u}r die G1-Phase relevanten Cycline D und E. Diese scheint sich erst posttranslational zu ereignen, da die unterschiedliche Expression auf mRNA-Ebene nicht festgestellt werden konnte. Zusammenfassend konnte dargestellt werden, dass die Infektion von Pharynxepithelzellen mit lebenden, zur Adh{\"a}renz und Invasion f{\"a}higen Meningokokkenst{\"a}mmen in der menschlichen Zielzelle einen Zellzyklusarrest in der G1-Phase verursacht, vermutlich durch ver{\"a}nderte Expression der Zellzyklusregulatoren p21WAF1/Cip1, Cyclin D und Cyclin E. M{\"o}glicherweise stellt die Induktion dieses Zellzyklusarrestes einen wichtigen Schritt in der Pathogenese der bakteriellen Kolonisation des oberen Atemwegsepithels durch N. meningitidis dar.}, subject = {Neisseria meningitidis}, language = {de} }