In April 2017, a rat was observed on an airplane during a flight from Miami (USA) to Berlin (Germany). After landing in Berlin, significant efforts were made to trap the rat and disinfect the airplane. As rats are known reservoir hosts for a variety of zoonotic pathogens, this event necessitated the establishment of a standard workflow for the detection of rodent-borne pathogens.
View Article and Find Full Text PDFPathogens have evolved to be highly adapted to their natural host. Community-associated methicillin-resistant USA300, for instance, is a lineage responsible for the epidemic of skin and soft tissue infections (SSTIs) in humans. Owing to its human tropism, mechanisms that enabled the rise of USA300 as a major skin pathogen remain incompletely defined.
View Article and Find Full Text PDFStaphylococci include both nasal commensals and opportunistic pathogens, globally responsible for a large proportion of infection-related deaths, especially in S. aureus carriers. To understand staphylococcal temporal dynamics within the nasal microbiota, we employed Staphylococcus-targeted sequencing in two cohorts from Denmark and Germany.
View Article and Find Full Text PDFis a versatile pathogen, renowned for its arsenal of virulence and immune evasion factors. Several virulence factors have been targeted in vaccination trials; however, so far, without success. Promising new vaccine candidates are the staphylococcal serine protease-like proteins (Spl A-F), which are involved in the pathogenesis and immune evasion of .
View Article and Find Full Text PDFAntibodies play a pivotal role in the immune defense and long-term immunity. Yet, while several studies have highlighted the persistence of antigen-specific antibody responses, it is unclear whether this stems from the continuous production of the same clones or recurrent activation of B cells generating new clones. To examine the stability of the human antibody repertoire, we monitored the concentrations of the most abundant IgG1 clones in plasma samples of 11 healthy donors at nine sampling points over a year.
View Article and Find Full Text PDFBackground: The characterization of physiological immune signatures in a population-based cohort is a prerequisite for identifying pathological immune signatures associated with inflammatory or autoimmune diseases.
Methods: Here, 47 plasma cytokines, chemokines, and growth factors were quantified with a bead-based multiplex-assay (Merck HCYTA-60 K) using a FLEXMAP 3D™ instrument in 1175 individuals of the Study of Health in Pomerania (SHIP; TREND cohort, 532 men and 643 women, age: 20 to 81, BMI: 17.7 to 53.
Background: The serine protease like (Spl) proteases of are a family of six proteases whose function and impact on virulence are poorly understood. Here we propose alpha-1-antitrypsin (AAT), an important immunomodulatory serine protease inhibitor as target of SplD, E and F. AAT is an acute phase protein, interacting with many proteases and crucial for prevention of excess tissue damage by neutrophil elastase during the innate immune response to infections.
View Article and Find Full Text PDFMonitoring the seroprevalence of SARS-CoV-2 in children and adolescents can provide valuable information for effective SARS-CoV-2 surveillance, and thus guide vaccination strategies. In this study, we quantified antibodies against the spike S1 domains of several SARS-CoV-2 variants (wild-type, Alpha, Delta, and Omicron variants) as well as endemic human coronaviruses (HCoVs) in 1,309 children and adolescents screened between December 2020 and March 2023. Their antibody binding profiles were compared with those of 22 pre-pandemic samples from children and adolescents using an in-house Luminex-based Corona Array (CA).
View Article and Find Full Text PDFStaphylococcus aureus is a prevalent pathogen in pneumonia and harbors glycolipids, which may serve as molecular patterns in Mincle (macrophage-inducible C-type lectin)-dependent pathogen recognition. We examined the role of Mincle in lung defense against S aureus in wild-type (WT), Mincle knockout (KO), and Mincle transgenic (tg) mice. Two glycolipids, glucosyl-diacylglycerol (Glc-DAG) and diglucosyl-diacylglycerol (Glc2-DAG), were purified, of which only Glc-DAG triggered Mincle reporter cell activation and professional phagocyte responses.
View Article and Find Full Text PDFIntroduction: COVID-19 vaccines are highly effective in inducing protective immunity. While the serum antibody response to COVID-19 vaccination has been studied in depth, our knowledge of the underlying plasmablast and memory B cell (Bmem) responses is still incomplete. Here, we determined the antibody and B cell response to COVID-19 vaccination in a naïve population and contrasted it with the response to a single influenza vaccination in a primed cohort.
View Article and Find Full Text PDFThe prevalence of multidrug-resistant is of global concern, and vaccines are urgently needed. The iron-regulated surface determinant protein B (IsdB) of was investigated as a vaccine candidate because of its essential role in bacterial iron acquisition but failed in clinical trials despite strong immunogenicity. Here, we reveal an unexpected second function for IsdB in pathogen-host interaction: the bacterial fitness factor IsdB triggers a strong inflammatory response in innate immune cells via Toll-like receptor 4 and the inflammasome, thus acting as a novel pathogen-associated molecular pattern of .
View Article and Find Full Text PDFLife-threatening toxic shock syndrome is often caused by the superantigen toxic shock syndrome toxin-1 (TSST-1) produced by . A well-known risk factor is the lack of neutralizing antibodies. To identify determinants of the anti-TSST-1 antibody response, we examined 976 participants of the German population-based epidemiological Study of Health in Pomerania (SHIP-TREND-0).
View Article and Find Full Text PDF(1) Background: COVID-19 is often associated with significant long-term symptoms and disability, i.e., the long/post-COVID syndrome (PCS).
View Article and Find Full Text PDFEBioMedicine
September 2022
Background: Understanding how SARS-CoV-2 affects respiratory centres in the brainstem may help to preclude assisted ventilation for patients in intensive care setting. Viral invasion appears unlikely, although autoimmunity has been implicated, the responsible antigens remain unknown. We previously predicted the involvement of three epitopes within distinct brainstem proteins: disabled homolog 1 (DAB1), apoptosis-inducing-factor-1 (AIFM1), and surfeit-locus-protein-1 (SURF1).
View Article and Find Full Text PDFMethicillin-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 S.
View Article and Find Full Text PDFVaccination 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).
View Article and Find Full Text PDFDue to increasing mupirocin resistance, alternatives for 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 and therefore exert less selection pressure. We identified promising adhesion inhibitors by screening a library of 4208 compounds for their capacity to inhibit adhesion to A-549 epithelial cells in vitro in a novel automated, imaging-based assay.
View Article and Find Full Text PDFFront Immunol
September 2021
Our goal was to provide a comprehensive overview of the antibody response to antigens in the general population as a basis for defining disease-specific profiles and diagnostic signatures. We tested the specific IgG and IgA responses to 79 staphylococcal antigens in 996 individuals from the population-based Study of Health in Pomerania. Using a dilution-based multiplex suspension array, we extended the dynamic range of specific antibody detection to seven orders of magnitude, allowing the precise quantification of high and low abundant antibody specificities in the same sample.
View Article and Find Full Text PDFWe asked whether transient in the oral environment synergistically interacts with orally associated bacterial species such as , , , , , and (six-species control biofilm 6S). For this purpose, four modified biofilms with seven species that contain either the wild type strain of the genotype (USA300-MRSA WT), its isogenic mutant with MSCRAMM deficiency (USA300-MRSA ΔMSCRAMM), a methicillin-sensitive (ST72-MSSA-) or a methicillin-resistant (USA800-MRSA) grown on hydroxyapatite disks were examined. Culture analyses, confocal-laser-scanning microscopy and proteome analyses were performed.
View Article and Find Full Text PDF() is a pathobiont of humans as well as a multitude of animal species. The high prevalence of multi-resistant and more virulent strains of necessitates the development of new prevention and treatment strategies for infection. Major advances towards understanding the pathogenesis of diseases have been made using conventional mouse models, i.
View Article and Find Full Text PDFcan cause life-threatening diseases, and hospital- as well as community-associated antibiotic-resistant strains are an emerging global public health problem. Therefore, prophylactic vaccines or immune-based therapies are considered as alternative treatment opportunities. To develop such novel treatment approaches, a better understanding of the bacterial virulence and immune evasion mechanisms and their potential effects on immune-based therapies is essential.
View Article and Find Full Text PDFsuperantigens (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 ; they comprise the toxic shock syndrome toxin (TSST-1), as well as 25 staphylococcal enterotoxins (SEs) or enterotoxin-like proteins (SEls).
View Article and Find Full Text PDFRats are a reservoir of human- and livestock-associated methicillin-resistant (MRSA). However, the composition of the natural population in wild and laboratory rats is largely unknown. Here, 144 nasal isolates from free-living wild rats, captive wild rats and laboratory rats were genotyped and profiled for antibiotic resistances and human-specific virulence genes.
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