11 results on '"Sybille Welker"'
Search Results
2. Emergence of Macrolide-Resistant Mycoplasma pneumoniae during an Outbreak in a Primary School: Clinical Characterization of Hospitalized Children
- Author
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Daniel Hubert, Roger Dumke, Stefan Weichert, Sybille Welker, Tobias Tenenbaum, and Horst Schroten
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Mycoplasma pneumoniae ,outbreak ,children ,macrolide resistance ,Medicine - Abstract
Mycoplasma pneumoniae (M. pneumoniae) is a common causative pathogen of community-acquired pneumonia. Here, we report the development of macrolide resistance during a school outbreak of severe M. pneumoniae infections in southwest Germany. We conducted a case series to assess the clinical and laboratory characteristics of hospitalized children with M. pneumonia infection and the prevalence of macrolide-resistant M. pneumoniae (MRMP) in this patient group. We retrospectively analyzed 23 children with serologically (19 patients) and/or PCR (eight patients) confirmed M. pneumoniae infection between October 2019 and December 2019. Most of the 15 hospitalized patients had lower respiratory tract infection (n = 10) and required oxygen therapy (83%). The median length of hospitalization was 7 days (range 3–10 days). In 8/15 patients (53.3%) azithromycin and in 4/15 (26.6%) clarithromycin treatment was applied. However, among the five patients for which extended molecular characterization was performed, sequencing of 23S rRNA revealed no mutation only in the first case, but development of macrolide resistance A2058G in four subsequent cases. Hence, we identified a cluster of hospitalized patients with emerging MRMP. Further studies are warranted to confirm a potential link between macrolide resistance and disease severity.
- Published
- 2021
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3. A case series of severe breakthrough infections observed in nine patients with COVID-19 in a southwestern German university hospital
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Bettina Lange, Sybille Welker, Maximilian Kittel, Claude Jabbour, Wolfgang Reindl, Thomas Walter, and Alexandra Heininger
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Microbiology (medical) ,Hospitals, University ,Infectious Diseases ,COVID-19 Vaccines ,SARS-CoV-2 ,COVID-19 ,Humans ,General Medicine ,Communicable Diseases ,BNT162 Vaccine ,Aged - Abstract
Vaccination is the key element for protection against COVID-19. Increased vaccination breakthroughs raise the question of whether additional prevention is necessary in case of individual risk factors for a severe course with hospitalization or death despite vaccination.Since July 13, 2021, there is an extended reporting requirement by German law. We analyzed our hospitalized patients with vaccine breakthrough infection during the first 8 weeks.Nine of 67 patients (13.4%) hospitalized for COVID-19 (median age 75 years) were fully vaccinated. Five of these patients received intensive care; two patients died. All had received two doses of BNT162b2 vaccines (Pfizer-BioNTech). There was a median of 99 days between complete immunization and symptom onset. All patients suffered from ≥ three comorbidities. Six patients (66.7%) showed a negative Anti-SARS-CoV-2-N titer at the time of vaccine breakthrough, five of these also had Anti-SARS-CoV-2-S titers 100 U/ml. All determinable cases were Delta variant B.1.617.2.Advanced age, underlying cardiorespiratory disease, and the Delta variant of SARS-CoV-2 were associated with hospitalization of our patients, suffering from vaccine breakthrough infection. Avoidance of face masks, lack of immunization of close contacts, and travel to high-risk areas have been observed as modifiable behavioural circumstances. Consistent personal protective measures, vaccination of close caregivers, and increased awareness might be effective measures in addition to COVID-19 booster vaccination for patients at a high risk to suffer a severe course of infection.
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- 2021
4. Rapid, adaptable and sensitive Cas13-based COVID-19 diagnostics using ADESSO
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Beatrice Casati, Joseph Peter Verdi, Alexander Hempelmann, Maximilian Kittel, Andrea Gutierrez Klaebisch, Bianca Meister, Sybille Welker, Sonal Asthana, Salvatore Di Giorgio, Pavle Boskovic, Ka Hou Man, Meike Schopp, Paul Adrian Ginno, Bernhard Radlwimmer, Charles Erec Stebbins, Thomas Miethke, Fotini Nina Papavasiliou, and Riccardo Pecori
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Multidisciplinary ,COVID-19 Testing ,SARS-CoV-2 ,General Physics and Astronomy ,COVID-19 ,Humans ,RNA, Viral ,General Chemistry ,Pandemics ,Sensitivity and Specificity ,General Biochemistry, Genetics and Molecular Biology - Abstract
During the ongoing COVID-19 pandemic, PCR testing and antigen tests have proven critical for helping to stem the spread of its causative agent, SARS-CoV-2. However, these methods suffer from either general applicability and/or sensitivity. Moreover, the emergence of variant strains creates the need for flexibility to correctly and efficiently diagnose the presence of substrains. To address these needs we developed the diagnostic test ADESSO (Accurate Detection of Evolving SARS-CoV-2 through SHERLOCK (Specific High Sensitivity Enzymatic Reporter UnLOCKing) Optimization) which employs Cas13 to diagnose patients in 1 h without sophisticated equipment. Using an extensive panel of clinical samples, we demonstrate that ADESSO correctly identifies infected individuals at a sensitivity and specificity comparable to RT-qPCR on extracted RNA and higher than antigen tests for unextracted samples. Altogether, ADESSO is a fast, sensitive and cheap method that can be applied in a point of care setting to diagnose COVID-19 and can be quickly adjusted to detect new variants.
- Published
- 2021
5. ADESSO: a rapid, adaptable and sensitive Cas13-based COVID-19 diagnostic platform
- Author
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Beatrice Casati, Joseph Peter Verdi, Alexander Hempelmann, Maximilian Kittel, Andrea Gutierrez Klaebisch, Bianca Meister, Sybille Welker, Sonal Asthana, Pavle Boskovic, Ka Hou Man, Meike Schopp, Paul Ginno, Bernhard Radlwimmer, Charles Erec Stebbins, Thomas Miethke, Fotini Nina Papavasiliou, and Riccardo Pecori
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education.field_of_study ,Coronavirus disease 2019 (COVID-19) ,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ,Population ,Diagnostic test ,Gold standard (test) ,Biology ,medicine.disease_cause ,Virology ,medicine ,CRISPR ,education ,Viral load ,Coronavirus - Abstract
With the coronavirus disease 19 (COVID-19) pandemic now deep into its second year, widespread testing for the detection of the causative severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is fundamental. The gold standard reverse transcription quantitative PCR (RT-qPCR) cannot keep up with the high demand alone, therefore alternative diagnostic tests are needed. Here we present ADESSO (Accurate Detection of Evolving SARS-CoV-2 through SHERLOCK Optimisation), an optimised version of the CRISPR-based SHERLOCK (Specific High-sensitivity Enzymatic Reporter unLOCKing) assay. After an extensive validation on 983 clinical samples, we demonstrated that ADESSO has a sensitivity of 96% and a specificity of 100% on extracted RNA, comparable to RT-qPCR. Its performance on unextracted samples still allows the detection of the more infectious 75% of the COVID-19 positive population, making it suitable for point-of-care (POC) testing. Interestingly, our in parallel comparison of 390 matching swab and gargle samples showed consistently lower viral loads in gargle specimens. We also validated ADESSO for the detection of the B.1.1.7 variant and demonstrated that ADESSO is adaptable to any variant of concern in less than one week, a critical feature now that worrisome SARS-CoV-2 variants are spreading all around the world.
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- 2021
6. Emergence of Macrolide-Resistant Mycoplasma pneumoniae during an Outbreak in a Primary School: Clinical Characterization of Hospitalized Children
- Author
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Roger Dumke, Stefan Weichert, Tobias Tenenbaum, Horst Schroten, Sybille Welker, and Daniel Hubert
- Subjects
Microbiology (medical) ,medicine.medical_specialty ,Mycoplasma pneumoniae ,macrolide resistance ,lcsh:Medicine ,Disease cluster ,medicine.disease_cause ,Azithromycin ,children ,Internal medicine ,Clarithromycin ,Lower respiratory tract infection ,Immunology and Allergy ,Medicine ,Molecular Biology ,Pathogen ,General Immunology and Microbiology ,outbreak ,business.industry ,lcsh:R ,Outbreak ,medicine.disease ,Pneumonia ,Infectious Diseases ,business ,medicine.drug - Abstract
Mycoplasma pneumoniae (M. pneumoniae) is a common causative pathogen of community-acquired pneumonia. Here, we report the development of macrolide resistance during a school outbreak of severe M. pneumoniae infections in southwest Germany. We conducted a case series to assess the clinical and laboratory characteristics of hospitalized children with M. pneumonia infection and the prevalence of macrolide-resistant M. pneumoniae (MRMP) in this patient group. We retrospectively analyzed 23 children with serologically (19 patients) and/or PCR (eight patients) confirmed M. pneumoniae infection between October 2019 and December 2019. Most of the 15 hospitalized patients had lower respiratory tract infection (n = 10) and required oxygen therapy (83%). The median length of hospitalization was 7 days (range 3–10 days). In 8/15 patients (53.3%) azithromycin and in 4/15 (26.6%) clarithromycin treatment was applied. However, among the five patients for which extended molecular characterization was performed, sequencing of 23S rRNA revealed no mutation only in the first case, but development of macrolide resistance A2058G in four subsequent cases. Hence, we identified a cluster of hospitalized patients with emerging MRMP. Further studies are warranted to confirm a potential link between macrolide resistance and disease severity.
- Published
- 2021
7. Emergence of carbapenem-resistant ST131
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Sybille, Welker, Sébastien, Boutin, Thomas, Miethke, Klaus, Heeg, and Dennis, Nurjadi
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Adult ,OXA-244 ,carbapenem resistance ,biochemical phenomena, metabolism, and nutrition ,Middle Aged ,Escherichia coli ST131 ,Young Adult ,Enterobacterales ,Carbapenems ,Germany ,Drug Resistance, Bacterial ,polycyclic compounds ,Escherichia coli ,bacteria ,Humans ,antimicrobial resistance ,Child ,Escherichia coli Infections ,Rapid Communication ,Aged - Abstract
The dissemination of carbapenem-producing Gram-negative bacteria is a major public health concern. We report the first detection of OXA-244-producing ST131 O16:H5 Escherichia coli in three patients from two tertiary hospitals in the south-west of Germany. OXA-244 is emerging in Europe. Because of detection challenges, OXA-244-producing E. coli may be under-reported. The emergence of carbapenem resistance in a globally circulating high-risk clone, such as ST131 E. coli is of clinical relevance and should be monitored closely.
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- 2020
8. Emergence of carbapenem-resistant ST131 Escherichia coli carrying blaOXA-244 in Germany, 2019 to 2020
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Sébastien Boutin, Thomas Miethke, Sybille Welker, Klaus Heeg, and Dennis Nurjadi
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0301 basic medicine ,Carbapenem resistant ,Epidemiology ,030106 microbiology ,Public Health, Environmental and Occupational Health ,Clone (cell biology) ,biochemical phenomena, metabolism, and nutrition ,Biology ,medicine.disease_cause ,biology.organism_classification ,Microbiology ,03 medical and health sciences ,030104 developmental biology ,Antibiotic resistance ,Virology ,Enterobacterales ,polycyclic compounds ,medicine ,bacteria ,Escherichia coli ,Bacteria ,Carbapenem resistance - Abstract
The dissemination of carbapenem-producing Gram-negative bacteria is a major public health concern. We report the first detection of OXA-244-producing ST131 O16:H5 Escherichia coli in three patients from two tertiary hospitals in the south-west of Germany. OXA-244 is emerging in Europe. Because of detection challenges, OXA-244-producing E. coli may be under-reported. The emergence of carbapenem resistance in a globally circulating high-risk clone, such as ST131 E. coli is of clinical relevance and should be monitored closely.
- Published
- 2020
9. Reconstitution of mRNA Editing in Yeast Using a Gal4-ApoB-Gal80 Fusion Transcript as the Selectable Marker
- Author
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J Greeve, Ines Diehl, Heinrich Lellek, Sybille Welker, and Romy Kirsten
- Subjects
Enzyme complex ,Saccharomyces cerevisiae Proteins ,Transcription, Genetic ,Apolipoprotein B ,APOBEC-1 Deaminase ,RNA-binding protein ,digestive system ,Biochemistry ,Fungal Proteins ,Catalytic Domain ,Cytidine Deaminase ,Yeasts ,Molecular Biology ,Selectable marker ,Apolipoproteins B ,biology ,Alternative splicing ,RNA-Binding Proteins ,Cell Biology ,Cytidine deaminase ,Molecular biology ,DNA-Binding Proteins ,Repressor Proteins ,RNA editing ,Trans-Activators ,biology.protein ,lipids (amino acids, peptides, and proteins) ,RNA Editing ,Transcription Factors - Abstract
We describe a fusion transcript of Gal4 linked to its specific inhibitor protein Gal80 by 276 nucleotides of apolipoprotein (apo) B sequence as a selectable marker for mRNA editing. Editing of apoB mRNA is catalyzed by an editing enzyme complex that introduces a stop codon by deamination of C to U. The catalytic subunit APOBEC-1 is a cytidine deaminase and requires a second essential component recently cloned and termed APOBEC-1 complementing factor (ACF) or APOBEC-1-stimulating protein (ASP). The aim of this study was to demonstrate that APOBEC-1 plus ACF/ASP comprise all that is required for editing of apoB mRNA in vivo. Expression of APOBEC-1 and Gal4 fused to its inhibitor Gal80 by an intervening unedited apoB sequence (Gal4-apoB(C)-Gal80) did not result in the Gal4-dependent expression of HIS3 and beta-galactosidase in the yeast strain CG1945. Co-expression of APOBEC-1 and ACF/ASP induced editing of the apoB site in up to 13% of the Gal4-apoB(C)-Gal80 transcripts and enabled selection of yeast cells for robust expression of HIS3 and beta-galactosidase. Additional expression of the alternative splicing regulatory protein KSRP increased the editing of the apoB site by APOBEC-1 and ACF/ASP to 21%. Thus, APOBEC-1 and ACF/ASP represent the core apoB mRNA editing enzyme in vivo. This study demonstrates for the first time the successful use of a selectable marker for mRNA editing. The Gal4-Gal80 system is analogous to the two-hybrid assay and may have broader applications for the study of other mRNA processing reactions.
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- 2002
10. Absence of APOBEC-1 mediated mRNA editing in human carcinomas
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Romy Kirsten, Katja Hundoegger, Heiner Greten, Heinrich Lellek, Sybille Welker, Jobst Greeve, Akbar Barialai, and Frank Apostel
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APOBEC ,Cancer Research ,Carcinoma, Hepatocellular ,Apolipoprotein B ,Arylamine N-Acetyltransferase ,RNA Splicing ,Bioinformatics ,medicine.disease_cause ,Catalytic Domain ,Genes, Neurofibromatosis 1 ,Genetics ,Carcinoma ,medicine ,Animals ,Humans ,RNA, Messenger ,RNA, Neoplasm ,RNA Processing, Post-Transcriptional ,Molecular Biology ,Apolipoproteins B ,Terminator Regions, Genetic ,biology ,Reverse Transcriptase Polymerase Chain Reaction ,Alternative splicing ,Liver Neoplasms ,medicine.disease ,Protein Structure, Tertiary ,Isoenzymes ,Cell Transformation, Neoplastic ,RNA editing ,Organ Specificity ,Hepatocellular carcinoma ,biology.protein ,Cancer research ,Rabbits ,Breast carcinoma ,Carcinogenesis - Abstract
The transgene expression of the catalytic subunit APOBEC-1 of the apo B mRNA editing enzyme-complex can cause hepatocellular carcinoma in mice and rabbits. It has been proposed that aberrant editing of mRNA may represent a novel oncogenic principle. This investigation aimed to define whether such aberrant hyperediting mediated by APOBEC-1 occurs in human carcinomas. Editing and hyperediting of apo B, NAT1 or NF1 mRNA was not identified in any of 28 resected tumor specimens, including hepatocellular, bile duct, gastric, colorectal, pancreatic adeno- and neuroendocrine, lung adeno-, medullary thyroid and breast carcinoma, soft tissue sarcoma and neuroblastoma. In most types of carcinoma, significant levels for full-length APOBEC-1 mRNA could not be detected. Low level expression of APOBEC-1 was found in colorectal and gastric carcinoma where most of the APOBEC-1 mRNA is inactivated by alternate splicing. The `auxiliary' components of the apo B mRNA editing enzyme-complex are missing in many tumors including colorectal and gastric carcinoma, but are highly expressed in hepatocellular, lung adeno- and breast carcinoma all of which lack APOBEC-1. Taken together, either APOBEC-1 or the `auxiliary' components of the apo B mRNA editing enzyme-complex or both are missing in human carcinomas resulting in the absence of mRNA editing. Currently, there is no evidence that aberrant editing mediated by APOBEC-1 contributes to the tumorigenesis of natural human carcinomas.
- Published
- 1999
11. Distinct promoters induce APOBEC-1 expression in rat liver and intestine
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Sybille Welker, David Axelos, Heiner Greten, J Greeve, and Meike Schipper
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Untranslated region ,Carcinoma, Hepatocellular ,Apolipoprotein B ,APOBEC-1 Deaminase ,Molecular Sequence Data ,Gene Expression ,Regulatory Sequences, Nucleic Acid ,Transfection ,Polymerase Chain Reaction ,Cytidine Deaminase ,Gene expression ,Tumor Cells, Cultured ,Animals ,Humans ,RNA, Messenger ,Intestinal Mucosa ,Promoter Regions, Genetic ,Apolipoproteins B ,biology ,Base Sequence ,Alternative splicing ,Liver Neoplasms ,Promoter ,Exons ,Molecular biology ,Rats ,Liver ,Regulatory sequence ,RNA editing ,biology.protein ,lipids (amino acids, peptides, and proteins) ,RNA Editing ,Cardiology and Cardiovascular Medicine - Abstract
Abstract —The expression of apolipoprotein (apo) B can be modulated by mRNA editing, a unique posttranscriptional base change in the apo B mRNA. Apo B-48, the translation product of edited apo B mRNA, is not a precursor of the atherogenic low density lipoproteins and lipoprotein(a). In humans and various other mammals, the apo B mRNA is edited in the intestine but not in the liver, which exclusively secretes apo B-100–containing lipoproteins as precursors for low density lipoprotein formation. In species such as the rat, mouse, dog, and horse, apo B mRNA is also edited in the liver, resulting in low plasma levels of low density lipoprotein. Editing of the apo B mRNA is mediated by the apo B mRNA–editing enzyme complex, of which the catalytic subunit APOBEC-1 is not expressed in the liver of species without hepatic editing. To understand the molecular basis for liver-specific expression of APOBEC-1 and the editing of hepatic apo B mRNA, the expression pattern and genomic organization of the rat APOBEC-1 gene have been characterized. The rat APOBEC-1 gene contains 6 exons and 2 promoters with distinct activities. The expression of APOBEC-1 in the rat liver is the result of a promoter located upstream, with tissue-specific exon use and alternate splicing within the 5′-untranslated region of APOBEC-1 mRNA encoded by exon 2. In addition to the liver, this promoter also induces APOBEC-1 expression in the spleen, lung, kidney, heart, and skeletal muscle. The promoter located downstream belongs to a new class of TATA-less promoters and is responsible for the abundant expression of APOBEC-1 in the intestine. Mapping of the transcriptional start sites and deletion analysis of the promoter regions by using luciferase as the reporter gene have defined the regulatory elements of both promoters. The downstream, intestine-specific promoter contains a negative regulatory element between −1100 and −500, which appears to restrict its activity to the intestine. The upstream, liver-specific promoter of the rat APOBEC-1 gene induces APOBEC-1 expression and editing of apo B mRNA in human hepatoma HuH-7 and Hep G2 cells. Understanding the molecular basis for the liver-specific expression of APOBEC-1 in the rat promises new strategies to induce APOBEC-1 expression in the human liver for the reduction of atherogenic lipoprotein levels by hepatic apo B mRNA editing.
- Published
- 1998
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