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Staphylococcus aureus (S. aureus) is a dangerous pathogen in and outside hospitals. However, much more commonly, the pathobiont behaves as an innocuous member of the human microbiome of the nose, skin or gastrointestinal tract, and in most people the immune system can control the opportunist for life. The equilibrium is based on multiple interactions between pathogen and host, which are well adapted to each other, and it can only be maintained at high cost to the immune system. Although S. aureus carriers gradually build up clinical protection, there appears to be no sterile immunity, and recurrent infections are common [1Wertheim HFL Melles DC Vos MC van Leeuwen W van Belkum A Verbrugh HA et al.The role of nasal carriage in Staphylococcus aureus infections.Lancet Infect Dis. 2005; 5: 751-762https://doi.org/10.1016/S1473-3099(05)70295-4Summary Full Text Full Text PDF PubMed Scopus (1575) Google Scholar, 2Eiff C von Becker K Machka K Stammer H Peters G Nasal carriage as a source of Staphylococcus aureus bacteremia. Study group.N Engl J Med. 2001; 344: 11-16https://doi.org/10.1056/NEJM200101043440102Crossref PubMed Scopus (1413) Google Scholar, 3Bröker BM Holtfreter S Bekeredjian-Ding I. Immune control of Staphylococcus aureus – regulation and counter-regulation of the adaptive immune response.Int J Med Microbiol. 2014; 304: 204-214https://doi.org/10.1016/j.ijmm.2013.11.008Crossref PubMed Scopus (44) Google Scholar]. In this issue of EBioMedicine, Jian-Dong Huang and coworkers add another facet to our knowledge of the fascinating interplay between S. aureus and its human host, showing how the microorganism manipulates the inflammasome [[4]Deng J Zhang B-Z Chu H Wang X-L Wang Y Gong H-R et al.Adenosine synthase A contributes to recurrent Staphylococcus aureus infection by dampening protective immunity.EBioMedicine. 2021; 70103505https://doi.org/10.1016/j.ebiom.2021.103505Summary Full Text Full Text PDF PubMed Scopus (0) Google Scholar].
Murthy N. Darisipudi; Barbara M. Bröker. How S. aureus blinds the inflammasome to escape immune control. EBioMedicine 2021, 71, 1 .
AMA StyleMurthy N. Darisipudi, Barbara M. Bröker. How S. aureus blinds the inflammasome to escape immune control. EBioMedicine. 2021; 71 ():1.
Chicago/Turabian StyleMurthy N. Darisipudi; Barbara M. Bröker. 2021. "How S. aureus blinds the inflammasome to escape immune control." EBioMedicine 71, no. : 1.
Methicillin-resistant Staphylococcus aureus (MRSA) can colonize dental patients and students, however, studies on the prevalence of MRSA and methicillin-susceptible S. aureus (MSSA) among dental health care workers (DHCW) including use of personal protective equipment (PPE) are scarce. We conducted an observational study (StaphDent study) to (I) determine the prevalence of MRSA and MSSA colonization in DHCW in the region of Mecklenburg Western-Pomerania, Germany, (II) resolve the MSSA population structure to gain hints on possible transmission events between co-workers, and (III) clarify use of PPE. Nasal swabs were obtained from dentists (n = 149), dental assistants (n = 297) and other dental practice staff (n = 38). Clonal relatedness of MSSA isolates was investigated using spa typing and, in some cases, whole genome sequencing (WGS). PPE use was assessed by questionnaire. While 22.3% (108/485) of the participants were colonized with MSSA, MRSA was not detected. MSSA prevalence was not associated with size of dental practices, gender, age, or duration of employment. The identified 61 spa types grouped into 17 clonal complexes and four sequence types. Most spa types (n = 51) were identified only once. In ten dental practices one spa type occurred twice. WGS data analysis confirmed a close clonal relationship for 4/10 isolate pairs. PPE was regularly used by most dentists and assistants. To conclude, the failure to recover MRSA from DHCW reflects the low MRSA prevalence in this region. Widespread PPE use suggests adherence to routine hygiene protocols. Compared to other regional HCW MRSA rates the consequent usage of PPE seems to be protective.
Nadine Lerche; Silva Holtfreter; Birgit Walther; Torsten Semmler; Fawaz Al’Sholui; Stephanie J. Dancer; Georg Daeschlein; Nils-Olaf Hübner; Barbara M. Bröker; Roald Papke; Thomas Kohlmann; Romy Baguhl; Ulrike Seifert; Axel Kramer. Staphylococcus aureus nasal colonization among dental health care workers in Northern Germany (StaphDent study). International Journal of Medical Microbiology 2021, 311, 151524 .
AMA StyleNadine Lerche, Silva Holtfreter, Birgit Walther, Torsten Semmler, Fawaz Al’Sholui, Stephanie J. Dancer, Georg Daeschlein, Nils-Olaf Hübner, Barbara M. Bröker, Roald Papke, Thomas Kohlmann, Romy Baguhl, Ulrike Seifert, Axel Kramer. Staphylococcus aureus nasal colonization among dental health care workers in Northern Germany (StaphDent study). International Journal of Medical Microbiology. 2021; 311 (6):151524.
Chicago/Turabian StyleNadine Lerche; Silva Holtfreter; Birgit Walther; Torsten Semmler; Fawaz Al’Sholui; Stephanie J. Dancer; Georg Daeschlein; Nils-Olaf Hübner; Barbara M. Bröker; Roald Papke; Thomas Kohlmann; Romy Baguhl; Ulrike Seifert; Axel Kramer. 2021. "Staphylococcus aureus nasal colonization among dental health care workers in Northern Germany (StaphDent study)." International Journal of Medical Microbiology 311, no. 6: 151524.
Vaccination using the adenoviral vector COVID-19 vaccine ChAdOx1 nCoV-19 (AstraZeneca) has been associated with rare vaccine-induced immune thrombotic thrombocytopenia (VITT). Affected patients test strongly positive in platelet factor 4 (PF4)/polyanion enzyme immunoassays (EIAs), and serum-induced platelet activation is maximal in the presence of PF4. We determined the frequency of anti-PF4/polyanion antibodies in healthy vaccinees and assessed whether PF4/polyanion EIA+ sera exhibit platelet-activating properties after vaccination with ChAdOx1 nCoV-19 (n = 138) or BNT162b2 (BioNTech/Pfizer; n = 143). In total, 19 of 281 participants tested positive for anti-PF4/polyanion antibodies postvaccination (All: 6.8% [95% confidence interval (CI), 4.4-10.3]; BNT162b2: 5.6% [95% CI, 2.9-10.7]; ChAdOx1 nCoV-19: 8.0% [95% CI, 4.5% to 13.7%]). Optical densities were mostly low (between 0.5 and 1.0 units; reference range, <0.50), and none of the PF4/polyanion EIA+ samples induced platelet activation in the presence of PF4. We conclude that positive PF4/polyanion EIAs can occur after severe acute respiratory syndrome coronavirus 2 vaccination with both messenger RNA- and adenoviral vector-based vaccines, but many of these antibodies likely have minor (if any) clinical relevance. Accordingly, low-titer positive PF4/polyanion EIA results should be interpreted with caution when screening asymptomatic individuals after vaccination against COVID-19. Pathogenic platelet-activating antibodies that cause VITT do not occur commonly following vaccination.
Thomas Thiele; Lena Ulm; Silva Holtfreter; Linda Schönborn; Sven Olaf Kuhn; Christian Scheer; Theodore E. Warkentin; Barbara M. Bröker; Karsten Becker; Konstanze Aurich; Kathleen Selleng; Nils-Olaf Hübner; Andreas Greinacher. Frequency of positive anti-PF4/polyanion antibody tests after COVID-19 vaccination with ChAdOx1 nCoV-19 and BNT162b2. Blood 2021, 138, 299 -303.
AMA StyleThomas Thiele, Lena Ulm, Silva Holtfreter, Linda Schönborn, Sven Olaf Kuhn, Christian Scheer, Theodore E. Warkentin, Barbara M. Bröker, Karsten Becker, Konstanze Aurich, Kathleen Selleng, Nils-Olaf Hübner, Andreas Greinacher. Frequency of positive anti-PF4/polyanion antibody tests after COVID-19 vaccination with ChAdOx1 nCoV-19 and BNT162b2. Blood. 2021; 138 (4):299-303.
Chicago/Turabian StyleThomas Thiele; Lena Ulm; Silva Holtfreter; Linda Schönborn; Sven Olaf Kuhn; Christian Scheer; Theodore E. Warkentin; Barbara M. Bröker; Karsten Becker; Konstanze Aurich; Kathleen Selleng; Nils-Olaf Hübner; Andreas Greinacher. 2021. "Frequency of positive anti-PF4/polyanion antibody tests after COVID-19 vaccination with ChAdOx1 nCoV-19 and BNT162b2." Blood 138, no. 4: 299-303.
Acute pancreatitis (AP) is an inflammatory disorder, the severe form of which is burdened with high mortality. The pathogenesis of severity-driving organ manifestations, such as respiratory and renal failure, is unknown. We used samples from 300 pancreatitis patients and an experimental model of severe acute pancreatitis (SAP) to characterize severity-dependent cytokine profiles and resident/circulating immune cell populations by flow-cytometry and real-time- fluorescence and deformability-cytometry analysis. On functional, immunolabelling and in-vivo antibody-depletion experiments we confirmed the role of inflammatory cells in pancreatitis but found neither T-cells, Ly6g+-neutrophils or granulocytic-myeloid-derived-suppressor-cells (gMDSC) but a massive mobilisation of CCR2+/CD11b+-monocytes to be responsible for lung and kidney injury during SAP. Real-time-fluorescence and deformability-cytometry analyses suggest, that the physical properties of monocytes, especially their large size, results in an obstruction of the fine capillary-systems of the lung or of the kidney glomeruli. Their selective depletion can represent a promising treatment strategy for pancreatitis as well as other inflammation-related disorders.
Anika Wilden; Juliane Glaubitz; Oliver Otto; Doreen Biedenweg; Matthias Nauck; Matthias Mack; Silvia Ribback; Barbara Bröker; Sabrina Freiin von Rheinbaben; Markus Lerch; Ali Aghdassi; Frank Weiss; Matthias Sendler. Obstruction of Capillaries by circulating large Monocytes causes Multi Organ Dysfunction Syndrome (MODS) in Acute Pancreatitis. 2021, 1 .
AMA StyleAnika Wilden, Juliane Glaubitz, Oliver Otto, Doreen Biedenweg, Matthias Nauck, Matthias Mack, Silvia Ribback, Barbara Bröker, Sabrina Freiin von Rheinbaben, Markus Lerch, Ali Aghdassi, Frank Weiss, Matthias Sendler. Obstruction of Capillaries by circulating large Monocytes causes Multi Organ Dysfunction Syndrome (MODS) in Acute Pancreatitis. . 2021; ():1.
Chicago/Turabian StyleAnika Wilden; Juliane Glaubitz; Oliver Otto; Doreen Biedenweg; Matthias Nauck; Matthias Mack; Silvia Ribback; Barbara Bröker; Sabrina Freiin von Rheinbaben; Markus Lerch; Ali Aghdassi; Frank Weiss; Matthias Sendler. 2021. "Obstruction of Capillaries by circulating large Monocytes causes Multi Organ Dysfunction Syndrome (MODS) in Acute Pancreatitis." , no. : 1.
Due to increasing mupirocin resistance, alternatives for Staphylococcus aureus nasal decolonization are urgently needed. Adhesion inhibitors are promising new preventive agents that may be less prone to induce resistance, as they do not interfere with the viability of S. aureus and therefore exert less selection pressure. We identified promising adhesion inhibitors by screening a library of 4208 compounds for their capacity to inhibit S. aureus adhesion to A-549 epithelial cells in vitro in a novel automated, imaging-based assay. The assay quantified DAPI-stained nuclei of the host cell; attached bacteria were stained with an anti-teichoic acid antibody. The most promising candidate, aurintricarboxylic acid (ATA), was evaluated in a novel persistent S. aureus nasal colonization model using a mouse-adapted S. aureus strain. Colonized mice were treated intranasally over 7 days with ATA using a wide dose range (0.5–10%). Mupirocin completely eliminated the bacteria from the nose within three days of treatment. In contrast, even high concentrations of ATA failed to eradicate the bacteria. To conclude, our imaging-based assay and the persistent colonization model provide excellent tools to identify and validate new drug candidates against S. aureus nasal colonization. However, our first tested candidate ATA failed to induce S. aureus decolonization.
Liliane Fernandes de Oliveira; Marina Steindorff; Murthy Darisipudi; Daniel Mrochen; Patricia Trübe; Barbara Bröker; Mark Brönstrup; Werner Tegge; Silva Holtfreter. Discovery of Staphylococcus aureus Adhesion Inhibitors by Automated Imaging and Their Characterization in a Mouse Model of Persistent Nasal Colonization. Microorganisms 2021, 9, 631 .
AMA StyleLiliane Fernandes de Oliveira, Marina Steindorff, Murthy Darisipudi, Daniel Mrochen, Patricia Trübe, Barbara Bröker, Mark Brönstrup, Werner Tegge, Silva Holtfreter. Discovery of Staphylococcus aureus Adhesion Inhibitors by Automated Imaging and Their Characterization in a Mouse Model of Persistent Nasal Colonization. Microorganisms. 2021; 9 (3):631.
Chicago/Turabian StyleLiliane Fernandes de Oliveira; Marina Steindorff; Murthy Darisipudi; Daniel Mrochen; Patricia Trübe; Barbara Bröker; Mark Brönstrup; Werner Tegge; Silva Holtfreter. 2021. "Discovery of Staphylococcus aureus Adhesion Inhibitors by Automated Imaging and Their Characterization in a Mouse Model of Persistent Nasal Colonization." Microorganisms 9, no. 3: 631.
We asked whether transient Staphylococcus aureus in the oral environment synergistically interacts with orally associated bacterial species such as Actinomyces oris, Candida albicans, Fusobacterium nucleatum, Streptococcus oralis, Streptococcus mutans, and Veillonella dispar (six-species control biofilm 6S). For this purpose, four modified biofilms with seven species that contain either the wild type strain of the S. aureus genotype (USA300-MRSA WT), its isogenic mutant with MSCRAMM deficiency (USA300-MRSA ΔMSCRAMM), a methicillin-sensitive S. aureus (ST72-MSSA-) or a methicillin-resistant S. aureus (USA800-MRSA) grown on hydroxyapatite disks were examined. Culture analyses, confocal-laser-scanning microscopy and proteome analyses were performed. S. aureus strains affected the amount of supragingival biofilm-associated species differently. The deletion of MSCRAMM genes disrupted the growth of S. aureus and the distribution of S. mutans and S. oralis within the biofilms. In addition, S. aureus caused shifts in the number of detectable proteins of other species in the 6S biofilm. S. aureus (USA300-MRSA WT), aggregated together with early colonizers such as Actinomyces and streptococci, influenced the number of secondary colonizers such as Fusobacterium nucleatum and was involved in structuring the biofilm architecture that triggered the change from a homeostatic biofilm to a dysbiotic biofilm to the development of oral diseases.
Etyene Schnurr; Pune Paqué; Thomas Attin; Paolo Nanni; Jonas Grossmann; Silva Holtfreter; Barbara Bröker; Christian Kohler; Binh Diep; Apoena Ribeiro; Thomas Thurnheer. Staphylococcus aureus Interferes with Streptococci Spatial Distribution and with Protein Expression of Species within a Polymicrobial Oral Biofilm. Antibiotics 2021, 10, 116 .
AMA StyleEtyene Schnurr, Pune Paqué, Thomas Attin, Paolo Nanni, Jonas Grossmann, Silva Holtfreter, Barbara Bröker, Christian Kohler, Binh Diep, Apoena Ribeiro, Thomas Thurnheer. Staphylococcus aureus Interferes with Streptococci Spatial Distribution and with Protein Expression of Species within a Polymicrobial Oral Biofilm. Antibiotics. 2021; 10 (2):116.
Chicago/Turabian StyleEtyene Schnurr; Pune Paqué; Thomas Attin; Paolo Nanni; Jonas Grossmann; Silva Holtfreter; Barbara Bröker; Christian Kohler; Binh Diep; Apoena Ribeiro; Thomas Thurnheer. 2021. "Staphylococcus aureus Interferes with Streptococci Spatial Distribution and with Protein Expression of Species within a Polymicrobial Oral Biofilm." Antibiotics 10, no. 2: 116.
Staphylococcus aureus superantigens (SAgs) are among the most potent T cell mitogens known. They stimulate large fractions of T cells by cross-linking their T cell receptor with major histocompatibility complex class-II molecules on antigen presenting cells, resulting in T cell proliferation and massive cytokine release. To date, 26 different SAgs have been described in the species S. aureus; they comprise the toxic shock syndrome toxin (TSST-1), as well as 25 staphylococcal enterotoxins (SEs) or enterotoxin-like proteins (SEls). SAgs can cause staphylococcal food poisoning and toxic shock syndrome and contribute to the clinical symptoms of staphylococcal infection. In addition, there is growing evidence that SAgs are involved in allergic diseases. This review provides an overview on recent epidemiological data on the involvement of S. aureus SAgs and anti-SAg-IgE in allergy, demonstrating that being sensitized to SEs—in contrast to inhalant allergens—is associated with a severe disease course in patients with chronic airway inflammation. The mechanisms by which SAgs trigger or amplify allergic immune responses, however, are not yet fully understood. Here, we discuss known and hypothetical pathways by which SAgs can drive an atopic disease.
Goran Abdurrahman; Frieder Schmiedeke; Claus Bachert; Barbara M. Bröker; Silva Holtfreter. Allergy—A New Role for T Cell Superantigens of Staphylococcus aureus? Toxins 2020, 12, 176 .
AMA StyleGoran Abdurrahman, Frieder Schmiedeke, Claus Bachert, Barbara M. Bröker, Silva Holtfreter. Allergy—A New Role for T Cell Superantigens of Staphylococcus aureus? Toxins. 2020; 12 (3):176.
Chicago/Turabian StyleGoran Abdurrahman; Frieder Schmiedeke; Claus Bachert; Barbara M. Bröker; Silva Holtfreter. 2020. "Allergy—A New Role for T Cell Superantigens of Staphylococcus aureus?" Toxins 12, no. 3: 176.
While immunoglobulin (Ig) E is a prominent biomarker for early-onset, its levels are often elevated in non-allergic late-onset asthma. However, the pattern of IgE expression in the latter is mostly polyclonal, with specific IgEs low or below detection level albeit with an increased total IgE. In late-onset severe asthma patients, specific IgE to Staphylococcal enterotoxins (se-IgE) can frequently be detected in serum, and has been associated with asthma, with severe asthma defined by hospitalisations, oral steroid use and decrease in lung function. Recently, se-IgE was demonstrated to even predict the development into severe asthma with exacerbations over the next decade. Staphylococcus aureus manipulates the airway mucosal immunology at various levels via its proteins, including superantigens, serine-protease-like proteins (Spls), or protein A (SpA) and possibly others. Release of IL-33 from respiratory epithelium and activation of innate lymphoid cells (ILCs) via its receptor ST2, type 2 cytokine release from those ILCs and T helper (Th) 2 cells, mast cell degranulation, massive local B-cell activation and IgE formation, and finally eosinophil attraction with consequent release of extracellular traps, adding to the epithelial damage and contributing to disease persistence via formation of Charcot–Leyden crystals are the most prominent hallmarks of the manipulation of the mucosal immunity by S. aureus. In summary, S. aureus claims a prominent role in the orchestration of severe airway inflammation and in current and future disease severity. In this review, we discuss current knowledge in this field and outline the needs for future research to fully understand the impact of S. aureus and its proteins on asthma.
Claus Bachert; Marc Humbert; Nicola A. Hanania; Nan Zhang; Stephen Holgate; Roland Buhl; Barbara M. Bröker. Staphylococcus aureus and its IgE-inducing enterotoxins in asthma: current knowledge. European Respiratory Journal 2020, 55, 1901592 .
AMA StyleClaus Bachert, Marc Humbert, Nicola A. Hanania, Nan Zhang, Stephen Holgate, Roland Buhl, Barbara M. Bröker. Staphylococcus aureus and its IgE-inducing enterotoxins in asthma: current knowledge. European Respiratory Journal. 2020; 55 (4):1901592.
Chicago/Turabian StyleClaus Bachert; Marc Humbert; Nicola A. Hanania; Nan Zhang; Stephen Holgate; Roland Buhl; Barbara M. Bröker. 2020. "Staphylococcus aureus and its IgE-inducing enterotoxins in asthma: current knowledge." European Respiratory Journal 55, no. 4: 1901592.
Pancreatitis starts with primarily sterile local inflammation that induces systemic inflammatory response syndrome, followed by compensatory anti-inflammatory response syndrome (CARS). We investigated the mechanisms of these processes in mice and human serum. We induced severe acute pancreatitis by partial duct ligation with caerulein stimulation or intraperitoneal injection of l-arginine in mice with deletion of interleukin (IL)12B, NLRP3, or IL18 and in mice given MCC950, a small molecule inhibitor of the NLRP3-inflammasome. Pancreata were collected from mice and analyzed by histology, and cytokine levels were measured in serum samples. We measured activation of adaptive immune responses in mice with pancreatitis by flow cytometry analysis of T cells (CD25 and CD69) isolated from the spleen. Differentiation of T-helper (Th1) cells, Th2 cells, and T-regulatory cells was determined by nuclear staining for TBET, GATA3, and FOXP3. We performed transcriptome analysis of mouse lymph nodes and bone marrow-derived macrophages after incubation with acini. We measured levels of cytokines in serum samples from patients with mild and severe acute pancreatitis. Activation of the adaptive immune response in mice was initiated by macrophage-derived, caspase 1-processed cytokines and required activation of NLRP3 (confirmed in serum samples from patients with pancreatitis). Spleen cells from mice with pancreatitis had increases in Th2 cells but not in Th1 cells. Bone marrow-derived macrophages secreted IL1B and IL18, but not IL12, after co-incubation with pancreatic acini. T-cell activation and severity of acute pancreatitis did not differ significantly between IL12B-deficient and control mice. In contrast, NLRP3- or IL18-deficient mice had reduced activation of T cells and no increase in Th2 cell-mediated responses compared with control mice. The systemic type 2 immune response was mediated by macrophage-derived cytokines of the IL1 family. Specifically, IL18 induced a Th2 cell-mediated response in the absence of IL12. MCC950 significantly reduced neutrophil infiltration, T-cell activation, and disease severity in mice. In mice with severe pancreatitis, we found systemic inflammatory response syndrome and compensatory anti-inflammatory response syndrome developed in parallel. Infiltrating macrophages promote inflammation and simultaneously induce a Th2 cell-mediated response via IL18. Inhibition of NLRP3 reduces systemic inflammatory response syndrome and compensatory anti-inflammatory response syndrome and might be used to treat patients with severe pancreatitis.
Matthias Sendler; Cindy Van Den Brandt; Juliane Glaubitz; Anika Wilden; Janine Golchert; Frank Ulrich Weiss; Georg Homuth; Laura L. De Freitas Chama; Neha Mishra; Ujjwal Mukund Mahajan; Lukas Bossaller; Uwe Völker; Barbara Bröker; Julia Mayerle; Markus M. Lerch. NLRP3 Inflammasome Regulates Development of Systemic Inflammatory Response and Compensatory Anti-Inflammatory Response Syndromes in Mice With Acute Pancreatitis. Gastroenterology 2020, 158, 253 -269.e14.
AMA StyleMatthias Sendler, Cindy Van Den Brandt, Juliane Glaubitz, Anika Wilden, Janine Golchert, Frank Ulrich Weiss, Georg Homuth, Laura L. De Freitas Chama, Neha Mishra, Ujjwal Mukund Mahajan, Lukas Bossaller, Uwe Völker, Barbara Bröker, Julia Mayerle, Markus M. Lerch. NLRP3 Inflammasome Regulates Development of Systemic Inflammatory Response and Compensatory Anti-Inflammatory Response Syndromes in Mice With Acute Pancreatitis. Gastroenterology. 2020; 158 (1):253-269.e14.
Chicago/Turabian StyleMatthias Sendler; Cindy Van Den Brandt; Juliane Glaubitz; Anika Wilden; Janine Golchert; Frank Ulrich Weiss; Georg Homuth; Laura L. De Freitas Chama; Neha Mishra; Ujjwal Mukund Mahajan; Lukas Bossaller; Uwe Völker; Barbara Bröker; Julia Mayerle; Markus M. Lerch. 2020. "NLRP3 Inflammasome Regulates Development of Systemic Inflammatory Response and Compensatory Anti-Inflammatory Response Syndromes in Mice With Acute Pancreatitis." Gastroenterology 158, no. 1: 253-269.e14.
Here, we demonstrate a high-dynamic-range quantification of antibody binding to single antigens in a multiplexed suspension bead array format. Using a dilution-based approach and the newly developed data analysis tool the quantitative dynamic range is increased by three orders of magnitude in the selected samples. The strong increase in dynamic range results in a more robust data basis for downstream analyses.
Tanja C. Meyer; Frank Schmidt; Jörn Steinke; Barbara Bröker; Uwe Völker; Stephan Michalik. Technical report: xMAPr – High-dynamic-range (HDR) quantification of antigen-specific antibody binding. Journal of Proteomics 2019, 212, 103577 .
AMA StyleTanja C. Meyer, Frank Schmidt, Jörn Steinke, Barbara Bröker, Uwe Völker, Stephan Michalik. Technical report: xMAPr – High-dynamic-range (HDR) quantification of antigen-specific antibody binding. Journal of Proteomics. 2019; 212 ():103577.
Chicago/Turabian StyleTanja C. Meyer; Frank Schmidt; Jörn Steinke; Barbara Bröker; Uwe Völker; Stephan Michalik. 2019. "Technical report: xMAPr – High-dynamic-range (HDR) quantification of antigen-specific antibody binding." Journal of Proteomics 212, no. : 103577.
Critically ill patients frequently develop muscle atrophy and weakness in the intensive-care-unit setting [intensive care unit-acquired weakness (ICUAW)]. Sepsis, systemic inflammation, and acute-phase response are major risk factors. We reported earlier that the acute-phase protein serum amyloid A1 (SAA1) is increased and accumulates in muscle of ICUAW patients, but its relevance was unknown. Our objectives were to identify SAA1 receptors and their downstream signalling pathways in myocytes and skeletal muscle and to investigate the role of SAA1 in inflammation-induced muscle atrophy. We performed cell-based in vitro and animal in vivo experiments. The atrophic effect of SAA1 on differentiated C2C12 myotubes was investigated by analysing gene expression, protein content, and the atrophy phenotype. We used the cecal ligation and puncture model to induce polymicrobial sepsis in wild type mice, which were treated with the IкB kinase inhibitor Bristol-Myers Squibb (BMS)-345541 or vehicle. Morphological and molecular analyses were used to investigate the phenotype of inflammation-induced muscle atrophy and the effects of BMS-345541 treatment. The SAA1 receptors Tlr2, Tlr4, Cd36, P2rx7, Vimp, and Scarb1 were all expressed in myocytes and skeletal muscle. Treatment of differentiated C2C12 myotubes with recombinant SAA1 caused myotube atrophy and increased interleukin 6 (Il6) gene expression. These effects were mediated by Toll-like receptors (TLR) 2 and 4. SAA1 increased the phosphorylation and activity of the transcription factor nuclear factor 'kappa-light-chain-enhancer' of activated B-cells (NF-κB) p65 via TLR2 and TLR4 leading to an increased binding of NF-κB to NF-κB response elements in the promoter region of its target genes resulting in an increased expression of NF-κB target genes. In polymicrobial sepsis, skeletal muscle mass, tissue morphology, gene expression, and protein content were associated with the atrophy response. Inhibition of NF-κB signalling by BMS-345541 increased survival (28.6% vs. 91.7%, P < 0.01). BMS-345541 diminished inflammation-induced atrophy as shown by a reduced weight loss of the gastrocnemius/plantaris (vehicle: -21.2% and BMS-345541: -10.4%; P < 0.05), tibialis anterior (vehicle: -22.7% and BMS-345541: -17.1%; P < 0.05) and soleus (vehicle: -21.1% and BMS-345541: -11.3%; P < 0.05) in septic mice. Analysis of the fiber type specific myocyte cross-sectional area showed that BMS-345541 reduced inflammation-induced atrophy of slow/type I and fast/type II myofibers compared with vehicle-treated septic mice. BMS-345541 reversed the inflammation-induced atrophy program as indicated by a reduced expression of the atrogenes Trim63/MuRF1, Fbxo32/Atrogin1, and Fbxo30/MuSA1. SAA1 activates the TLR2/TLR4//NF-κB p65 signalling pathway to cause myocyte atrophy. Systemic inhibition of the NF-κB pathway reduced muscle atrophy and increased survival of septic mice. The SAA1/TLR2/TLR4//NF-κB p65 atrophy pathway could have utility in combatting ICUAW.
Alexander Hahn; Melanie Kny; Cristina Pablo‐Tortola; Mihail Todiras; Michael Willenbrock; Sibylle Schmidt; Katrin Schmoeckel; Ilka Jorde; Marcel Nowak; Ernst Jarosch; Thomas Sommer; Barbara Bröker; Stephan B. Felix; Claus Scheidereit; Steffen Weber‐Carstens; Christian Butter; Friedrich C. Luft; Jens Fielitz. Serum amyloid A1 mediates myotube atrophy via Toll‐like receptors. Journal of Cachexia, Sarcopenia and Muscle 2019, 11, 103 -119.
AMA StyleAlexander Hahn, Melanie Kny, Cristina Pablo‐Tortola, Mihail Todiras, Michael Willenbrock, Sibylle Schmidt, Katrin Schmoeckel, Ilka Jorde, Marcel Nowak, Ernst Jarosch, Thomas Sommer, Barbara Bröker, Stephan B. Felix, Claus Scheidereit, Steffen Weber‐Carstens, Christian Butter, Friedrich C. Luft, Jens Fielitz. Serum amyloid A1 mediates myotube atrophy via Toll‐like receptors. Journal of Cachexia, Sarcopenia and Muscle. 2019; 11 (1):103-119.
Chicago/Turabian StyleAlexander Hahn; Melanie Kny; Cristina Pablo‐Tortola; Mihail Todiras; Michael Willenbrock; Sibylle Schmidt; Katrin Schmoeckel; Ilka Jorde; Marcel Nowak; Ernst Jarosch; Thomas Sommer; Barbara Bröker; Stephan B. Felix; Claus Scheidereit; Steffen Weber‐Carstens; Christian Butter; Friedrich C. Luft; Jens Fielitz. 2019. "Serum amyloid A1 mediates myotube atrophy via Toll‐like receptors." Journal of Cachexia, Sarcopenia and Muscle 11, no. 1: 103-119.
Wie funktionieren Impfungen? Wir unterscheiden aktive und passive Vakzinierungen. Bei der aktiven Vakzinierung wird Antigen appliziert, das im Organismus eine adaptive Immunantwort auslöst. Dies benötigt Zeit, doch hält die Wirkung lange an, da ein antigenspezifisches Immungedächtnis aufgebaut wird. Bei der passiven Vakzinierung werden immunologische Effektormoleküle oder Immunzellen appliziert, die ihre Wirkung sofort entfalten.
Barbara Bröker; Christine Schütt; Bernhard Fleischer. Immunisierung. Grundwissen Immunologie 2019, 247 -254.
AMA StyleBarbara Bröker, Christine Schütt, Bernhard Fleischer. Immunisierung. Grundwissen Immunologie. 2019; ():247-254.
Chicago/Turabian StyleBarbara Bröker; Christine Schütt; Bernhard Fleischer. 2019. "Immunisierung." Grundwissen Immunologie , no. : 247-254.
Der Vielfalt der Erreger und ihres Verhaltens muss die Immunantwort angepasst sein, um ein Optimum in der Balance zwischen wirksamer Abwehr und unvermeidlichem Begleitschaden für den Organismus zu erzielen. Es sind folglich verschiedene Qualitäten der Immunantwort notwendig, wobei das Habitat der Infektionserregerdie optimale Abwehrstrategie bestimmt.
Barbara Bröker; Christine Schütt; Bernhard Fleischer. Wie schützt das Immunsystem bei Infektionen? Grundwissen Immunologie 2019, 157 -171.
AMA StyleBarbara Bröker, Christine Schütt, Bernhard Fleischer. Wie schützt das Immunsystem bei Infektionen? Grundwissen Immunologie. 2019; ():157-171.
Chicago/Turabian StyleBarbara Bröker; Christine Schütt; Bernhard Fleischer. 2019. "Wie schützt das Immunsystem bei Infektionen?" Grundwissen Immunologie , no. : 157-171.
Dialysis patients are frequently exposed to Staphylococcus aureus due to stays in dialysis centers, hospitals or rest homes. The hemodialysis vascular access is a potential entry site for S. aureus, in particular when using a central venous catheter (CVC) which increases the risk of sepsis compared to arteriovenous (AV) fistula. We prospectively followed a cohort of 86 hemodialysis patients from an outpatient dialysis center over 25 months analyzing S. aureus carrier status, S. aureus infection rates and mortality. Demographic data and patients´ medical histories were collected and followed from all hemodialysis patients. Blood samples, nasal swabs and swabs from the hemodialysis vascular access site were taken every six months for a period of 25 months and tested for S. aureus. Strains were cultured and further characterized by spa PCR and microarray-based genotyping. Resulting data were compared with those from the general population. In cross-sectional analyses, an average of 40% of hemodialysis patients were S. aureus carriers compared to 27% in the general population. Longitudinally, a total of 65% were S. aureus carriers: 16% were persistent carriers, 43% were intermittently colonized. The most common S. aureus lineage in the dialysis patient cohort was the clonal complex (CC) 8 and the spa type t008, while in the general population, the clonal complex CC30 dominates. During the study period, we observed six S. aureus-associated blood stream infections with one S. aureus attributable death. S. aureus carriers with an AV fistula were more densely colonized in the nasal mucosa compared to patients with a CVC. Overall mortality was lower for hemodialysis patients with a positive S. aureus carrier status compared to non-carriers (hazard ratio of 0.19). Compared to the general population, hemodialysis patients were more frequently colonized with S. aureus and displayed both different S. aureus colonization densities as well as lineages, possibly explained by more frequent exposure to health care environments. The lower overall mortality in carriers compared to non-carriers is intriguing and will be investigated in detail in the future. ISRCTN 14385893 , 2. October 2018, retrospectively registered.
Matthias Scheuch; Sabrina Freiin Von Rheinbaben; Antje Kabisch; Jonas Engeßer; Susanne Ahrendt; Thomas Dabers; Christian Kohler; Silva Holtfreter; Barbara M. Bröker; Sylvia Stracke. Staphylococcus aureus colonization in hemodialysis patients: a prospective 25 months observational study. BMC Nephrology 2019, 20, 153 .
AMA StyleMatthias Scheuch, Sabrina Freiin Von Rheinbaben, Antje Kabisch, Jonas Engeßer, Susanne Ahrendt, Thomas Dabers, Christian Kohler, Silva Holtfreter, Barbara M. Bröker, Sylvia Stracke. Staphylococcus aureus colonization in hemodialysis patients: a prospective 25 months observational study. BMC Nephrology. 2019; 20 (1):153.
Chicago/Turabian StyleMatthias Scheuch; Sabrina Freiin Von Rheinbaben; Antje Kabisch; Jonas Engeßer; Susanne Ahrendt; Thomas Dabers; Christian Kohler; Silva Holtfreter; Barbara M. Bröker; Sylvia Stracke. 2019. "Staphylococcus aureus colonization in hemodialysis patients: a prospective 25 months observational study." BMC Nephrology 20, no. 1: 153.
SBackgroundObesity has become a severe problem among the world’s population with clearly increasing prevalence over the last decades. Because obesity is associated with several comorbidities (e.g. hypertension or cancer) it constitutes an increasing burden for the health care system. Correlations between obesity and cognition have been studied in humans with ambivalent results. Here, we studied the effects of obesity on hippocampus dependent learning and memory and cell morphology in a mouse model of obesity.MethodsThe body mass of male and female Lep+/+(wt) and Lepob/ob(ob/ob) animals with access to food and water ad libitum was measured between postnatal day 60-200 and animals with clear adiposity (4-6 months) were further analyzed. Adult hippocampal neurogenesis in the dentate gyrus was examined using phosphohistone H3 as a marker for proliferation, doublecortin as a marker for differentiation and caspase3 as a marker for apoptosis. Moreover, the density of dendritic spines on apical and basal dendrites of pyramidal neurons of the cornu ammonis 1 (CA1) were analyzed using Golgi impregnation. In addition, mice were subjected to the open field and Morris water maze test in order to analyze locomotor activity and spatial learning.ResultsThe body weight of ob/ob mice nearly doubled during the first 120 postnatal days. Adult hippocampal neurogenesis was reduced in ob/ob mice due to reduced cell proliferation. Dendritic spine densities in the hippocampal area CA1 were not altered in ob/ob mice. Four to six months old ob/ob mice showed reduced locomotor activity in the open field test but similar performance in the Morris water maze compared to control mice.ConclusionOur data show that alterations in adult neurogenesis in leptin-deficient mice are not associated with an impairment in spatial learning abilities. Moreover, ob/ob mice are inconspicuous in the Morris water maze and do not display altered spine densities in the hippocampus, suggesting that obesity does not have a severe impact upon hippocampal neuronal plasticity and spatial learning.
Alexander Bracke; Grazyna Domanska; Katharina Bracke; Steffen Harzsch; Jens Van Den Brandt; Barbara Broeker; Oliver Von Bohlen Und Halbach. Obesity alters mobility and adult neurogenesis, but not hippocampal dependent learning in ob/ob mice. 2019, 537720 .
AMA StyleAlexander Bracke, Grazyna Domanska, Katharina Bracke, Steffen Harzsch, Jens Van Den Brandt, Barbara Broeker, Oliver Von Bohlen Und Halbach. Obesity alters mobility and adult neurogenesis, but not hippocampal dependent learning in ob/ob mice. . 2019; ():537720.
Chicago/Turabian StyleAlexander Bracke; Grazyna Domanska; Katharina Bracke; Steffen Harzsch; Jens Van Den Brandt; Barbara Broeker; Oliver Von Bohlen Und Halbach. 2019. "Obesity alters mobility and adult neurogenesis, but not hippocampal dependent learning in ob/ob mice." , no. : 537720.
Jens Schreiber; Barbara Bröker; Rainer Ehmann; Claus Bachert. Nonatopic severe asthma might still be atopic: Sensitization toward Staphylococcus aureus enterotoxins. Journal of Allergy and Clinical Immunology 2019, 143, 2279 -2280.e2.
AMA StyleJens Schreiber, Barbara Bröker, Rainer Ehmann, Claus Bachert. Nonatopic severe asthma might still be atopic: Sensitization toward Staphylococcus aureus enterotoxins. Journal of Allergy and Clinical Immunology. 2019; 143 (6):2279-2280.e2.
Chicago/Turabian StyleJens Schreiber; Barbara Bröker; Rainer Ehmann; Claus Bachert. 2019. "Nonatopic severe asthma might still be atopic: Sensitization toward Staphylococcus aureus enterotoxins." Journal of Allergy and Clinical Immunology 143, no. 6: 2279-2280.e2.
Currently, it is controversially discussed whether a relationship between obesity and cognition exists. We here analyzed a mouse model of obesity (leptin-deficient mice) to study the effects of obesity on the morphology of the hippocampus (a brain structure involved in mechanisms related to learning and memory) and on behavior. Mice aged 4 to 6 months were analyzed. At this age, the obese mice have nearly double the body weight as controls, but display smaller brains (brain volume is about 10% smaller) as control animals of the same age. Adult hippocampal neurogenesis, a process that is linked to learning and memory, might be disturbed in the obese mice and contribute to the smaller brain volume. Adult hippocampal neurogenesis was examined using specific markers for cell proliferation (phosphohistone H3), neuronal differentiation (doublecortin), and apoptosis (caspase 3). The number of phosphohistone H3 and doublecortin-positive cells was markedly reduced in leptin-deficient mice, but not the number of apoptotic cells, indicating that adult hippocampal neurogenesis on the level of cell proliferation was affected. In addition, dendritic spine densities of pyramidal neurons in the hippocampal area CA1 were analyzed using Golgi impregnation. However, no significant change in dendritic spine densities was noted in the obese mice. Moreover, the performance of the mice was analyzed in the open field as well as in the Morris water maze. In the open field test, obese mice showed reduced locomotor activity, but in the Morris water maze they showed similar performance compared with control animals.
Alexander Bracke; Grazyna Domanska; Katharina Bracke; Steffen Harzsch; Jens Van Den Brandt; Barbara Bröker; Oliver Von Bohlen Und Halbach. Obesity Impairs Mobility and Adult Hippocampal Neurogenesis. Journal of Experimental Neuroscience 2019, 13, 1 .
AMA StyleAlexander Bracke, Grazyna Domanska, Katharina Bracke, Steffen Harzsch, Jens Van Den Brandt, Barbara Bröker, Oliver Von Bohlen Und Halbach. Obesity Impairs Mobility and Adult Hippocampal Neurogenesis. Journal of Experimental Neuroscience. 2019; 13 ():1.
Chicago/Turabian StyleAlexander Bracke; Grazyna Domanska; Katharina Bracke; Steffen Harzsch; Jens Van Den Brandt; Barbara Bröker; Oliver Von Bohlen Und Halbach. 2019. "Obesity Impairs Mobility and Adult Hippocampal Neurogenesis." Journal of Experimental Neuroscience 13, no. : 1.
Staphylococcus (S.) aureus is a leading cause of bacterial infection world-wide, and currently no vaccine is available for humans. Vaccine development relies heavily on clinically relevant infection models. However, the suitability of mice for S. aureus infection models has often been questioned, because experimental infection of mice with human-adapted S. aureus requires very high infection doses. Moreover, mice were not considered to be natural hosts of S. aureus. The latter has been disproven by our recent findings, showing that both laboratory mice, as well as wild small mammals including mice, voles, and shrews, are naturally colonized with S. aureus. Here, we investigated whether mouse-and vole-derived S. aureus strains show an enhanced virulence in mice as compared to the human-adapted strain Newman. Using a step-wise approach based on the bacterial genotype and in vitro assays for host adaptation, we selected the most promising candidates for murine infection models out of a total of 254 S. aureus isolates from laboratory mice as well as wild rodents and shrews. Four strains representing the clonal complexes (CC) 8, 49, and 88 (n = 2) were selected and compared to the human-adapted S. aureus strain Newman (CC8) in murine pneumonia and bacteremia models. Notably, a bank vole-derived CC49 strain, named DIP, was highly virulent in BALB/c mice in pneumonia and bacteremia models, whereas the other murine and vole strains showed virulence similar to or lower than that of Newman. At one tenth of the standard infection dose DIP induced disease severity, bacterial load and host cytokine and chemokine responses in the murine bacteremia model similar to that of Newman. In the pneumonia model, DIP was also more virulent than Newman but the effect was less pronounced. Whole genome sequencing data analysis identified a pore-forming toxin, LukF-PV(P83)/LukM, in DIP but not the other tested S. aureus isolates. To conclude, the mouse-adapted S. aureus strain DIP allows a significant reduction of the inoculation dose in mice and is hence a promising tool to develop clinically more relevant infection models.
Patricia Trübe; Tobias Hertlein; Daniel M. Mrochen; Daniel Schulz; Ilka Jorde; Bettina Krause; Julia Zeun; Stefan Fischer; Silver A. Wolf; Birgit Walther; Torsten Semmler; Barbara Bröker; Rainer G. Ulrich; Knut Ohlsen; Silva Holtfreter. Bringing together what belongs together: Optimizing murine infection models by using mouse-adapted Staphylococcus aureus strains. International Journal of Medical Microbiology 2018, 309, 26 -38.
AMA StylePatricia Trübe, Tobias Hertlein, Daniel M. Mrochen, Daniel Schulz, Ilka Jorde, Bettina Krause, Julia Zeun, Stefan Fischer, Silver A. Wolf, Birgit Walther, Torsten Semmler, Barbara Bröker, Rainer G. Ulrich, Knut Ohlsen, Silva Holtfreter. Bringing together what belongs together: Optimizing murine infection models by using mouse-adapted Staphylococcus aureus strains. International Journal of Medical Microbiology. 2018; 309 (1):26-38.
Chicago/Turabian StylePatricia Trübe; Tobias Hertlein; Daniel M. Mrochen; Daniel Schulz; Ilka Jorde; Bettina Krause; Julia Zeun; Stefan Fischer; Silver A. Wolf; Birgit Walther; Torsten Semmler; Barbara Bröker; Rainer G. Ulrich; Knut Ohlsen; Silva Holtfreter. 2018. "Bringing together what belongs together: Optimizing murine infection models by using mouse-adapted Staphylococcus aureus strains." International Journal of Medical Microbiology 309, no. 1: 26-38.
Staphylococcus aureus (S. aureus) is a dangerous pathogen as well as a frequent colonizer, threatening human health worldwide. Protection against S. aureus infection is challenging, as the bacteria have sophisticated strategies to escape the host immune response. To maintain equilibrium with S. aureus, both innate and adaptive immune effector mechanisms are required. Dendritic cells (DCs) are critical players at the interface between the two arms of the immune system, indispensable for inducing specific T cell responses. In this review, we highlight the importance of DCs in mounting innate as well as adaptive immune responses against S. aureus with emphasis on their role in S. aureus-induced respiratory diseases. We also review what is known about mechanisms that S. aureus has adopted to evade DCs or manipulate these cells to its advantage.
Murthy N. Darisipudi; Maria Nordengrün; Barbara M. Bröker; Vincent Péton. Messing with the Sentinels—The Interaction of Staphylococcus aureus with Dendritic Cells. Microorganisms 2018, 6, 87 .
AMA StyleMurthy N. Darisipudi, Maria Nordengrün, Barbara M. Bröker, Vincent Péton. Messing with the Sentinels—The Interaction of Staphylococcus aureus with Dendritic Cells. Microorganisms. 2018; 6 (3):87.
Chicago/Turabian StyleMurthy N. Darisipudi; Maria Nordengrün; Barbara M. Bröker; Vincent Péton. 2018. "Messing with the Sentinels—The Interaction of Staphylococcus aureus with Dendritic Cells." Microorganisms 6, no. 3: 87.
Most Staphylococcus aureus strains secrete two lipases SAL1 and SAL2 encoded by gehA and gehB. These two lipases differ with respect to their substrate specificity. Staphylococcus hyicus secretes another lipase, SHL, which is in contrast to S. aureus lipases Ca2+-dependent and has a broad-spectrum lipase and phospholipase activity. The aim of this study was to investigate the role of staphylococcal (phospho) lipases in virulence. For this we constructed a gehA-gehB double deletion mutant in S. aureus USA300 and expressed SHL in agr-positive (accessory gene regulator) and agr-negative S. aureus strains. The lipases themselves have no hemolytic or cytotoxic activity. However, in agr-negative strains SHL-expression caused an upregulation of hemolytic activity. We further show that SHL-expression significantly enhanced biofilm formation probably due to an increase of extracellular DNA release. SHL-expression also increased host cell invasion 4-6-fold. Trioleate, a main triacylglycerol component of mammalian skin, induced lipase production. Finally, in the mouse sepsis and skin colonization models the lipase producing and mutant strain showed no significant difference compared to the WT strain. In conclusion, we show that staphylococcal lipases promote biofilm formation and host cell invasion and thereby contribute to S. aureus virulence.
Minh-Thu Nguyen; Arif Luqman; Katharina Bitschar; Tobias Hertlein; Johannes Dick; Knut Ohlsen; Barbara Bröker; Birgit Schittek; Friedrich Götz. Staphylococcal (phospho)lipases promote biofilm formation and host cell invasion. International Journal of Medical Microbiology 2018, 308, 653 -663.
AMA StyleMinh-Thu Nguyen, Arif Luqman, Katharina Bitschar, Tobias Hertlein, Johannes Dick, Knut Ohlsen, Barbara Bröker, Birgit Schittek, Friedrich Götz. Staphylococcal (phospho)lipases promote biofilm formation and host cell invasion. International Journal of Medical Microbiology. 2018; 308 (6):653-663.
Chicago/Turabian StyleMinh-Thu Nguyen; Arif Luqman; Katharina Bitschar; Tobias Hertlein; Johannes Dick; Knut Ohlsen; Barbara Bröker; Birgit Schittek; Friedrich Götz. 2018. "Staphylococcal (phospho)lipases promote biofilm formation and host cell invasion." International Journal of Medical Microbiology 308, no. 6: 653-663.