A5045116743- Bacterial biofilms and quorum sensing
- Click Chemistry and Applications
- Bacterial Genetics and Biotechnology
- Biochemical and Structural Characterization
- Chemical Synthesis and Analysis
- Peptidase Inhibition and Analysis
- Microbial Natural Products and Biosynthesis
- Antimicrobial Resistance in Staphylococcus
- Antibiotic Resistance in Bacteria
- Bacteriophages and microbial interactions
- Image Retrieval and Classification Techniques
- Microbial Community Ecology and Physiology
- Antimicrobial Peptides and Activities
- Protist diversity and phylogeny
- Advanced Image and Video Retrieval Techniques
- Computational Drug Discovery Methods
- Mosquito-borne diseases and control
- Genomics and Phylogenetic Studies
- Legume Nitrogen Fixing Symbiosis
- Planetary Science and Exploration
- RNA and protein synthesis mechanisms
- Insect symbiosis and bacterial influences
- Biotin and Related Studies
- Plant Pathogenic Bacteria Studies
- Invertebrate Immune Response Mechanisms
University of Vienna
2020-2025
University of Konstanz
2015-2023
RWTH Aachen University
2022
Ecologie Microbienne Lyon
2020
Brandenburg University of Technology Cottbus-Senftenberg
2012-2015
Anstalt für Verbrennungskraftmaschinen List (Germany)
2011-2014
Harvard University
2011-2014
University of Rostock
2014
Technical University of Munich
2010-2011
Center for Integrated Protein Science Munich
2008-2010
To approach the daunting problem of multidrug resistant bacterial pathogens, a multidisciplinary chemical proteomic strategy was applied and functionalized β-lactones were identified as potent, cell permeable inhibitors for specific selective targeting key virulence regulator complex ClpP in S. aureus methicillin (MRSA) strains. represents central protease responsible activation numerous factors including many with devastating effects human health such hemolysins, proteases, lipases, DNases....
A chemical proteomic strategy has been applied directly to bacterial proteomes, and β-lactones have identified as important natural product derivatives with a high affinity various enzyme classes (see picture). This approach may serve potent tool for the identification of novel antibacterial targets, study their function, definition lead structures design inhibitors. Supporting information this article is available on WWW under http://www.wiley-vch.de/contents/jc_2002/2008/z705768_s.pdf or...
Biofilms are often associated with human bacterial infections, and the natural tolerance of biofilms to antibiotics challenges treatment. Compounds antibiofilm activity could become useful adjuncts antibiotic therapy. We used norspermidine, a trigger for biofilm disassembly in developmental cycle Bacillus subtilis, develop guanidine biguanide compounds up 20-fold increased potency preventing formation breaking down existing biofilms. These also were active against pathogenic Staphylococcus...
A framework for molecular complexity is established that based on information theory and consistent with chemical knowledge. The resulting index Cm derived from abstracting the content of a molecule by degrees freedom in microenvironments per-atom basis, allowing to be calculated simple additive way. This allows any universally assessed sensitive stereochemistry, heteroatoms, symmetry. performance this evaluated compared against current state art. Its character gives values also very large...
Finding the target: Activity-based proteomic profiling probes based on depalmitoylation inhibitors palmostatin B and M (see picture) have been synthesized were found to target acyl protein thioesterase 1 (APT1) 2 (APT2) in cells.
Caseinolytic protease P (ClpP) represents a central bacterial degradation machinery that is involved in cell homeostasis and pathogenicity. The functional role of ClpP has been studied by genetic knockouts through the use beta-lactones, which remain only specific inhibitors discovered to date. Beta-lactones have served as chemical tools manipulate several organisms; however, their potency, selectivity stability limited. Despite detailed structural insights into composition conformational...
The Clp proteolytic machinery has important functions in many bacteria such as L. monocytogenes. Some organisms encode for two uncharacterized ClpP isoforms. Vibralactone was used to study the activity and assembly of ClpP1 ClpP2 subunits a hetero-oligomeric complex. Electron microscopic images reveal that tetradecameric is made up stacked homoheptameric rings. Detailed facts importance specialist readers are published "Supporting Information". Such documents peer-reviewed, but not...
A "breathing" protein: The first structure of the virulence regulator and heat shock protein ClpP from Staphylococcus aureus reveals a previously unobserved compressed state barrel. conformational switch in active center "handle region" results closure sites opening equatorial pores. These confirm proposed modes processive substrate degradation product release for protease family.
Activity-based protein profiling (ABPP) employs small molecule probes to profile their dedicated targets in complex proteomes. Unlike traditional proteomics which is limited on abundance, that selectively target the active site of certain proteins are a benign measure activity and provide tools for functional analysis. ABPP have largely replaced isotope labelled demonstrated broad spectrum utility ranging from identification characterization disease associated enzymes drug development....
Showdomycin is a potent nucleoside antibiotic that displays high structural similarity to uridine and pseudouridine. No detailed target analysis of this very unusual electrophilic natural product has been carried out so far. To unravel its biological function, we synthesized showdomycin probe can be appended with fluorophor or biotin marker via click chemistry identified diverse enzymes which were important for either the viability virulence pathogenic bacteria. Our results indicate effect...
Catch me if you can: The ClpP protease mediates protein homeostasis and can be efficiently inhibited by β-lactones. A combination of molecular docking, mutagenesis, activity-based profiling, kinetics studies now reveals the mechanism inhibition. hydrophobic pocket next to active site allows binding long aliphatic aromatic residues. preferred stereoisomer binds into oxyanion hole. As a service our authors readers, this journal provides supporting information supplied authors. Such materials...
Abstract Some bacteria swarm under some circumstances; they move rapidly and collectively over a surface. In an effort to understand the molecular signals controlling swarming, we isolated two bacterial strains from same red seaweed, Vibrio alginolyticus B522, vigorous swarmer, Shewanella algae B516, which inhibits V. swarming in its vicinity. Plate assays combined with NMR, MS, X‐ray diffraction analyses identified small molecule, was named avaroferrin, as potent inhibitor. Avaroferrin,...
Abstract The pathogen Pseudomonas aeruginosa produces over 50 different quinolones, 16 of which belong to the class 2‐alkyl‐4‐quinolone N ‐oxides (AQNOs) with various chain lengths and degrees saturation. We present first synthesis a previously proposed unsaturated compound that is confirmed be in culture extracts P . , its structure shown trans‐Δ 1 ‐2‐(non‐1‐enyl)‐4‐quinolone ‐oxide. This most active agent against S. aureus including MRSA strains, by more than one order magnitude whereas...
Bacteriophages have major impact on their microbial hosts and shape entire communities. The majority of these phages are latent reside as prophages integrated in the genomes hosts. A variety intricate regulatory systems determine switch from a lysogenic to lytic life style, but so far strategies lacking selectively control prophage induction by small molecules. Here we show that Pseudomonas aeruginosa deploys trigger factor hijack polylysogenic Staphylococcus aureus strain causing selective...
Disarmed forces: Inhibition of the central virulence regulator ClpP by structurally refined beta-lactones resulted in dramatically reduced production devastating factors, including pyrogenic toxin superantigens derived from pathogenic multiresistant Staphylococcus aureus strains. Targeting this could present an attractive strategy for neutralizing harmful effects bacterial pathogens, and help host immune response to eliminate disarmed bacteria.
Abstract Many human-targeted drugs alter the gut microbiome, leading to implications for host health. However, mechanisms underlying these effects are not well known. Here we combined quantitative microbiome profiling, long-read metagenomics, stable isotope probing and single-cell chemical imaging investigate impact of two widely prescribed on microbiome. Physiologically relevant concentrations entacapone, a treatment Parkinson’s disease, or loxapine succinate, used treat schizophrenia, were...
Abstract Background Given the global rise in antimicrobial resistance, discovery of novel agents and production processes thereof are utmost importance. To this end we have activated gene cluster encoding for biosynthesis potent antifungal compound ilicicolin H fungus Trichoderma reesei . While biosynthetic (BGC) is silent under standard cultivation conditions, achieved BGC activation by genetically overexpressing transcription factor TriliR. Results Successful was confirmed RT-qPCR,...
2-Alkyl-4(1H)-quinolones play a key role in bacterial communication, regulating biofilm formation, and virulence. Their antimicrobial properties also support survival interspecies competition microbial communities. In addition to the human pathogen Pseudomonas aeruginosa various species of Burkholderia Pseudoalteromonas are known produce 2-alkyl-4(1H)-quinolones. However, evolutionary relationships their biosynthetic gene clusters remain largely unexplored. To address this, we investigated...