A5028048641- Biochemical and Structural Characterization
- Microbial Natural Products and Biosynthesis
- Antimicrobial Resistance in Staphylococcus
- Antimicrobial Peptides and Activities
- Bacterial Genetics and Biotechnology
- Antibiotic Resistance in Bacteria
- RNA and protein synthesis mechanisms
- Genomics and Phylogenetic Studies
- Probiotics and Fermented Foods
- Bacteriophages and microbial interactions
- Bacterial biofilms and quorum sensing
- Marine Sponges and Natural Products
- Carbohydrate Chemistry and Synthesis
- Reproductive tract infections research
- SARS-CoV-2 detection and testing
- Lipid Membrane Structure and Behavior
- Insect symbiosis and bacterial influences
- Nanoparticle-Based Drug Delivery
- Chemical Synthesis and Analysis
- Microbial Metabolism and Applications
- Phagocytosis and Immune Regulation
- Biosensors and Analytical Detection
- Microbial Inactivation Methods
- X-ray Diffraction in Crystallography
- Clostridium difficile and Clostridium perfringens research
University of Bonn
2016-2025
University Hospital Bonn
2009-2025
German Center for Infection Research
2013-2024
University of Tübingen
2024
Evotec (Germany)
2023-2024
Roche (Switzerland)
2017-2022
Roche Pharma AG (Germany)
2020-2021
CS Diagnostics
2021
Charité - Universitätsmedizin Berlin
2014
Vivantes Klinikum
2014
Defining Defensins' Mode of Action Defensins are antimicrobial host defense peptides that play a role in innate immunity. Many such act by disrupting the bacterial membrane; however, Schneider et al. (p. 1168 ) now show fungal defensin, plecstasin, targets cell wall biosynthesis. Biochemical studies identified Lipid II as cellular target plecstasin and residues involved complex formation were using NMR spectroscopy computational modeling. Initial two defensins from invertebrates also II....
Daptomycin is a highly efficient last-resort antibiotic that targets the bacterial cell membrane. Despite its clinical importance, exact mechanism by which daptomycin kills bacteria not fully understood. Different experiments have led to different models, including (i) blockage of wall synthesis, (ii) membrane pore formation, and (iii) generation altered curvature leading aberrant recruitment proteins. To determine model correct, we carried out comprehensive mode-of-action study using...
Abstract The lipopeptide daptomycin is used as an antibiotic to treat severe infections with gram-positive pathogens, such methicillin resistant Staphylococcus aureus (MRSA) and drug-resistant enterococci. Its precise mechanism of action incompletely understood, a specific molecular target has not been identified. Here we show that Ca 2+ -daptomycin specifically interacts undecaprenyl-coupled cell envelope precursors in the presence anionic phospholipid phosphatidylglycerol, forming...
Antimicrobial resistance is a leading mortality factor worldwide. Here, we report the discovery of clovibactin, an antibiotic isolated from uncultured soil bacteria. Clovibactin efficiently kills drug-resistant Gram-positive bacterial pathogens without detectable resistance. Using biochemical assays, solid-state nuclear magnetic resonance, and atomic force microscopy, dissect its mode action. blocks cell wall synthesis by targeting pyrophosphate multiple essential peptidoglycan precursors...
Human beta-defensin 3 (hBD3) is a highly charged (+11) cationic host defense peptide, produced by epithelial cells and neutrophils. hBD3 retains antimicrobial activity against broad range of pathogens, including multiresistant Staphylococcus aureus, even under high-salt conditions. Whereas peptides are assumed to act permeabilizing cell membranes, the transcriptional response pattern hBD3-treated staphylococcal resembled that vancomycin-treated (V. Sass, U. Pag, A. Tossi, G. Bierbaum, H....
Summary Staphylococcus aureus peptidoglycan is cross‐linked via a characteristic pentaglycine interpeptide bridge. Genetic analysis had identified three peptidyltransferases, FemA, FemB and FemX, to catalyse the formation of bridge, using glycyl t‐RNA as Gly donor. To analyse bridge in vitro , we purified potential substrates for UDP‐MurNAc‐pentapeptide, lipid I II staphylococcal pool, well His‐tagged Gly‐tRNA‐synthetase FemX. We found that FemX used exclusively acceptor first residue....
ABSTRACT Friulimicin B is a naturally occurring cyclic lipopeptide, produced by the actinomycete Actinoplanes friuliensis , with excellent activity against gram-positive pathogens, including multidrug-resistant strains. It consists of macrocyclic decapeptide core and lipid tail, interlinked an exocyclic amino acid. water soluble amphiphilic, overall negative charge. Amphiphilicity enhanced in presence Ca 2+ which also indispensable for antimicrobial activity. shares these physicochemical...
ABSTRACT The activity of lanthionine-containing peptide antibiotics (lantibiotics) is based on different killing mechanisms which may be combined in one molecule. prototype lantibiotic nisin inhibits peptidoglycan synthesis and forms pores through specific interaction with the cell wall precursor lipid II. Gallidermin epidermin possess same putative II binding motif as nisin; however, both peptides are considerably shorter (22 amino acids, compared to 34 nisin). We demonstrate that model...
The peptidoglycan of Staphylococcus aureus is characterized by a high degree crosslinking and almost completely lacks free carboxyl groups, due to amidation the D-glutamic acid in stem peptide. Amidation has been proposed play decisive role polymerization cell wall building blocks, correlating with neighboring peptides. Mutants reduced are less viable show increased susceptibility methicillin. We identified enzymes catalyzing formation D-glutamine position 2 provide biochemical evidence that...
Abstract Lantibiotics are ribosomally synthesized and post‐translationally modified peptides (RiPPs) characterized by the presence of lanthionine or methyllanthionine rings their antimicrobial activity. Cacaoidin, a novel glycosylated lantibiotic, was isolated from Streptomyces cacaoi strain fully NMR, mass spectrometry, chemical derivatization approaches genome analysis. The new molecule combines outstanding structural features, such as high number d ‐amino acids, an uncommon tyrosine...
Abstract The Gram-positive cell wall consists of peptidoglycan functionalized with anionic glycopolymers, such as teichoic acid and capsular polysaccharide (CP). How the different polymers are assembled in a coordinated fashion is not fully understood. Here, we reconstitute Staphylococcus aureus CP biosynthesis elucidate its interplay biosynthetic machinery. We show that CapAB tyrosine kinase complex controls multiple enzymatic checkpoints through reversible phosphorylation to modulate...
Frequently bacteria are exposed to membrane-damaging cationic antimicrobial molecules (CAMs) produced by the host's immune system (defensins, cathelicidins) or competing microorganisms (bacteriocins). Staphylococcus aureus achieves CAM resistance modifying anionic phosphatidylglycerol with positively charged L-lysine, resulting in repulsion of peptides. Inactivation novel S. gene, mprF, which is found many bacterial pathogens, has resulted loss lysylphosphatidylglycerol (L-PG), increased...
ABSTRACT Teixobactin represents the first member of a newly discovered class antibiotics that act through inhibition cell wall synthesis. binds multiple bactoprenol-coupled precursors, inhibiting both peptidoglycan and teichoic acid Here, we show impressive bactericidal activity teixobactin is due to synergistic targets, resulting in damage, delocalization autolysins, subsequent lysis. We also find does not bind mature peptidoglycan, further increasing its at high densities against...
Antimicrobial peptides are a new class of antibiotics that promising for pharmaceutical applications because they have retained efficacy throughout evolution. One antimicrobial the defensins, which been found in different species. Here we describe fungal defensin, eurocin. Eurocin acts against range Gram-positive human pathogens but not Gram-negative bacteria. consists 42 amino acids, forming cysteine-stabilized α/β-fold. The thermal denaturation data point shows disulfide bridges being...