Publications by authors named "Leif Steil"

Introduction: is a human pathobiont that asymptomatically colonizes the upper respiratory tract but can cause severe diseases such as pneumonia, sepsis, and meningitis, as well as non-invasive infections like otitis media and sinusitis. It thrives in the nutrient-limited environment of the nasopharynx and has evolved mechanisms to manage host-induced stress and regulate protein levels accordingly.

Methods: To investigate the molecular biology of under in vitro and infection-relevant conditions, a suitable cultivation medium is essential for reproducible experiments.

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is 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 .

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The Gram-positive opportunistic pathogen colonizes ∼30% of the human population but also causes various diseases. Precise regulation of genes involved in virulence and metabolic functions is required to adapt to changing host conditions, such as severe restriction of iron availability. In addition to the global regulator Fur (ferric uptake regulator), the iron limitation response of is shaped by the recently identified sRNA IsrR (iron sparing response regulator).

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Background: Recombinant proteins facilitate and contribute to detailed studies of the virulence mechanisms and pathophysiology of the major human pathogen Staphylococcus aureus. Of particular interest are secreted virulence factors. However, due to their potential toxicity and specific post-translational processing, virulence factors are difficult targets for heterologous protein production.

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Thrombosis and thrombocytopenia syndromes (TTS) describe immune-mediated thrombotic adverse reactions after vaccination against COVID-19. Vaccine-induced immune thrombotic thrombocytopenia (VITT) is a well-known subentity of TTS, caused by adenovirus vector-based vaccines. VITT is mediated by anti-platelet factor 4 (PF4) immunoglobulin G (IgG) antibodies, activating platelets via Fc-γ IIa receptors (FcγRIIa).

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Staphylococcus aureus is a Gram-positive opportunistic pathogen that has colonized nearly 30% of the human population and can cause life-threatening infections. S. aureus exports a variety of virulence factors, such as a novel set of extracellular serine protease-like proteins (Spls).

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Summary: Proteome studies frequently encounter challenges in down-stream data analysis due to limited bioinformatics resources, rapid data generation, and variations in analytical methods. To address these issues, we developed SpectroPipeR, an R package designed to streamline data analysis tasks and provide a comprehensive, standardized pipeline for Spectronaut® DIA-MS data. This novel package automates various analytical processes, including XIC plots, ID rate summary, normalization, batch and covariate adjustment, relative protein quantification, multivariate analysis, and statistical analysis, while generating interactive HTML reports for e.

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Acute pancreatitis (AP) is characterised by self-digestion of the pancreas by its own proteases. This pathophysiological initiating event in AP occurs inside pancreatic acinar cells where intrapancreatic trypsinogen becomes prematurely activated by cathepsin B (CTSB), and induces the digestive protease cascade, while cathepsin L (CTSL) degrades trypsin and trypsinogen and therefore prevents the development of AP. These proteases are located in the secretory compartment of acinar cells together with cystatin C (CST3), an endogenous inhibitor of CTSB and CTSL.

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Background: Atopic dermatitis (AD) is a chronic, relapsing inflammatory skin disease with skin barrier defects and a misdirected type 2 immune response against harmless antigens. The skin microbiome in AD is characterized by a reduction in microbial diversity with a dominance of staphylococci, including ().

Objective: To assess whether antigens play a role in AD, we screened for candidate allergens and studied the T cell and humoral immune response against the extracellular serine protease (Esp).

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ATP-binding cassette (ABC) transport systems are crucial for bacteria to ensure sufficient uptake of nutrients that are not produced de novo or improve the energy balance. The cell surface of the pathobiont Streptococcus pneumoniae (pneumococcus) is decorated with a substantial array of ABC transporters, critically influencing nasopharyngeal colonization and invasive infections. Given the auxotrophic nature of pneumococci for certain amino acids, the Ami ABC transporter system, orchestrating oligopeptide uptake, becomes indispensable in host compartments lacking amino acids.

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In the expanding market of recombinant proteins, microbial cell factories such as are key players. Microbial cell factories experience secretion stress during high-level production of secreted proteins, which can negatively impact product yield and cell viability. The CssRS two-component system and CssRS-regulated quality control proteases HtrA and HtrB play critical roles in the secretion stress response.

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In proteomics, fast, efficient, and highly reproducible sample preparation is of utmost importance, particularly in view of fast scanning mass spectrometers enabling analyses of large sample series. To address this need, we have developed the web application MassSpecPreppy that operates on the open science OT-2 liquid handling robot from Opentrons. This platform can prepare up to 96 samples at once, performing tasks like BCA protein concentration determination, sample digestion with normalization, reduction/alkylation and peptide elution into vials or loading specified peptide amounts onto Evotips in an automated and flexible manner.

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Vaccine-induced immune thrombotic thrombocytopenia (VITT; synonym, thrombosis with thrombocytopenia syndrome, is associated with high-titer immunoglobulin G antibodies directed against platelet factor 4 (PF4). These antibodies activate platelets via platelet FcγIIa receptors, with platelet activation greatly enhanced by PF4. Here we summarize the current concepts in the pathogenesis of VITT.

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Vector-based SARS-CoV-2 vaccines have been associated with vaccine- induced thrombosis with thrombocytopenia syndrome (VITT/TTS), but the causative factors are still unresolved. We comprehensively analyzed the ChAdOx1 nCoV-19 (AstraZeneca) and Ad26.COV2.

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Staphylococcus aureus is an opportunistic pathogen that can cause life-threatening infections, particularly in immunocompromised individuals. The high-level virulence of S. aureus largely relies on its diverse and variable collection of virulence factors and immune evasion proteins, including the six serine protease-like proteins SplA to SplF.

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SARS-CoV-2 vaccine ChAdOx1 nCoV-19 (AstraZeneca) causes a thromboembolic complication termed vaccine-induced immune thrombotic thrombocytopenia (VITT). Using biophysical techniques, mouse models, and analysis of VITT patient samples, we identified determinants of this vaccine-induced adverse reaction. Super-resolution microscopy visualized vaccine components forming antigenic complexes with platelet factor 4 (PF4) on platelet surfaces to which anti-PF4 antibodies obtained from VITT patients bound.

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The widely conserved twin-arginine translocases (Tat) allow the transport of fully folded cofactor-containing proteins across biological membranes. In doing so, these translocases serve different biological functions ranging from energy conversion to cell division. In the Gram-positive soil bacterium Bacillus subtilis, the Tat machinery is essential for effective growth in media lacking iron or NaCl.

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The Gram-positive bacterium Bacillus subtilis is frequently exposed to hyperosmotic conditions. In addition to the induction of genes involved in the accumulation of compatible solutes, high salinity exerts widespread effects on B. subtilis physiology, including changes in cell wall metabolism, induction of an iron limitation response, reduced motility and suppression of sporulation.

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The promising potential of cold atmospheric plasma (CAP) treatment as a new therapeutic option in the field of medicine, particularly in Otorhinolaryngology and Respiratory medicine, demands primarily the assessment of potential risks and the prevention of any direct and future cell damages. Consequently, the application of a special intensity of CAP that is well tolerated by cells and tissues is of particular interest. Although improvement of wound healing by CAP treatment has been described, the underlying mechanisms and the molecular influences on human tissues are so far only partially characterized.

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Epidemiological studies found an association between increased platelet size and the risk for thrombotic complications, but functional differences of large and small platelets remain poorly understood due to a lack of standardized protocols separating platelets with different size. We designed a protocol to separate large and small platelets from 15 mL whole blood. Separated large and small platelet fractions differed in mean platelet volume: 12.

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Circulating platelets consist of subpopulations with different age, maturation state and size. In this review, we address the association between platelet size and platelet function and summarize the current knowledge on platelet subpopulations including reticulated platelets, procoagulant platelets and platelets exposing signals to mediate their clearance. Thereby, we emphasize the impact of platelet turnover as an important condition for platelet production .

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The ProJ and ProH enzymes of Bacillus subtilis catalyse together with ProA (ProJ-ProA-ProH), osmostress-adaptive synthesis of the compatible solute proline. The proA-encoded gamma-glutamyl phosphate reductase is also used for anabolic proline synthesis (ProB-ProA-ProI). Transcription of the proHJ operon is osmotically inducible whereas that of the proBA operon is not.

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Understanding cellular life requires a comprehensive knowledge of the essential cellular functions, the components involved, and their interactions. Minimized genomes are an important tool to gain this knowledge. We have constructed strains of the model bacterium, Bacillus subtilis, whose genomes have been reduced by ∼36%.

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Unlabelled: Dilated cardiomyopathy (DCM) is a disease of the myocardium with reduced left ventricular ejection fraction (LVEF). Cardiac autoantibodies (AAbs) play a causal role in the development and progression of DCM. Removal of AAbs using immunoadsorption (IA/IgG) has been shown as a therapeutic option to improve cardiac function.

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