A5005651518- Bacterial Genetics and Biotechnology
- Antibiotic Resistance in Bacteria
- Genomics and Phylogenetic Studies
- Microbial Natural Products and Biosynthesis
- Antimicrobial Resistance in Staphylococcus
- Reproductive tract infections research
- Bacteriophages and microbial interactions
- Biochemical and Structural Characterization
- Glycosylation and Glycoproteins Research
- Metabolomics and Mass Spectrometry Studies
- RNA and protein synthesis mechanisms
- Enzyme Production and Characterization
- Clostridium difficile and Clostridium perfringens research
- Biochemical and Molecular Research
- Legume Nitrogen Fixing Symbiosis
- Toxin Mechanisms and Immunotoxins
- Drug-Induced Adverse Reactions
- Microscopic Colitis
- Herpesvirus Infections and Treatments
- Bacterial Identification and Susceptibility Testing
- Protein purification and stability
- Bacterial biofilms and quorum sensing
- Escherichia coli research studies
- Antimicrobial Peptides and Activities
- Monoclonal and Polyclonal Antibodies Research
University of Notre Dame
2016-2024
University Hospital Bonn
2023-2024
University of Bonn
2014-2024
University of Lausanne
2016
Kumasi Centre for Collaborative Research in Tropical Medicine
2016
University of Zurich
2016
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...
Muropeptides are a group of bacterial natural products generated from the cell wall in course its turnover. These compounds cell-wall recycling intermediates and also involved signaling within bacterium. However, identity these molecules remains elusive. The identification characterization 20 muropeptides Pseudomonas aeruginosa is described. least abundant metabolites present at 100 most 55,000 per Analysis under conditions induction resistance to β-lactam antibiotic identified two...
Antibiotic tolerance and antibiotic resistance are the two major obstacles to efficient reliable treatment of bacterial infections. Identifying adjuvants that sensitize resistant tolerant bacteria killing may lead development superior treatments with improved outcomes. Vancomycin, a lipid II inhibitor, is frontline for treating methicillin-resistant Staphylococcus aureus other Gram-positive However, vancomycin use has led increasing prevalence strains reduced susceptibility vancomycin. Here,...
Abstract SPOR domains are widely present in bacterial proteins that recognize cell-wall peptidoglycan strands stripped of the peptide stems. This type is enriched septal ring as a product catalysis by amidases participate separation daughter cells during cell division. Here, we document binding synthetic denuded glycan ligands to domain lytic transglycosylase RlpA from Pseudomonas aeruginosa (SPOR-RlpA) mass spectrometry and structural analyses, demonstrate indeed presence stems abrogates...
Intracellular Chlamydiaceae do not need to resist osmotic challenges and a functional cell wall was detected in these pathogens. Nevertheless, recent study revealed evidence for circular peptidoglycan-like structures penicillin inhibits cytokinesis, phenomenon known as the chlamydial anomaly. Here, by characterizing precursor-processing enzyme, we provide insights into mechanisms underlying this mystery. We show that AmiA from Chlamydia pneumoniae separates daughter cells an Escherichia coli...
For intracellular Chlamydiaceae, there is no need to withstand osmotic challenges, and a functional cell wall has not been detected in these pathogens so far. Nevertheless, penicillin inhibits division Chlamydiaceae resulting enlarged aberrant bodies, phenomenon known as chlamydial anomaly.D-alanine unique essential component the biosynthesis of bacterial walls. In free-living bacteria like Escherichia coli, penicillin-binding proteins such monofunctional transpeptidases PBP2 PBP3, putative...
About 100,000 deaths are attributed annually to infections with methicillin-resistant Staphylococcus aureus (MRSA) despite concerted efforts toward vaccine development and clinical trials involving several preclinically efficacious drug candidates. This necessitates the of alternative therapeutic options against this drug-resistant bacterial pathogen. Using Masuda borylation-Suzuki coupling (MBSC) sequence, we previously synthesized modified naturally occurring bisindole alkaloids, alocasin...
Gram-positive bacterial infections present a major clinical challenge, with methicillin- and vancomycin-resistant strains continuing to be cause for concern. In recent years, semisynthetic vancomycin derivatives have been developed overcome this problem as exemplified by the clinically used telavancin, which exhibits increased antibacterial potency but has also raised toxicity concerns. Thus, glycopeptide antibiotics enhanced activities improved safety profiles are still necessary. We...
The N-acetylglucosaminidase NagZ of Pseudomonas aeruginosa catalyzes the first cytoplasmic step in recycling muropeptides, cell-wall-derived natural products. This reaction regulates gene expression for β-lactam resistance enzyme, β-lactamase. enzyme hydrolysis N-acetyl-β-d-glucosamine-(1→4)-1,6-anhydro-N-acetyl-β-d-muramyl-peptide (1) to N-acetyl-β-d-glucosamine (2) and 1,6-anhydro-N-acetyl-β-d-muramyl-peptide (3). structural functional aspects catalysis by were investigated a total seven...
BglX is a heretofore uncharacterized periplasmic glycoside hydrolase (GH) of the human pathogen
Abstract The protein networks of cell-wall-biosynthesis assemblies are largely unknown. A key class enzymes in these is the lytic transglycosylases (LTs), which eleven exist P. aeruginosa . We have undertaken a pulldown strategy conjunction with mass-spectrometry-based proteomics to identify putative binding partners for LTs total 71 were identified LTs. systematic assessment rare lipoprotein (RlpA), one pseudomonal LTs, was made. This 37-kDa involved bacterial daughter-cell separation by an...
Antimicrobial resistance is a leading mortality factor worldwide. Here we report the discovery of clovibactin, new antibiotic, isolated from uncultured soil bacteria. Clovibactin efficiently kills drug-resistant bacterial pathogens without detectable resistance. Using biochemical assays, solid-state NMR, and atomic force microscopy, dissect its mode action. blocks cell wall synthesis by targeting pyrophosphate multiple essential peptidoglycan precursors (C 55 PP, Lipid II, WTA ). uses an...
β-Lactams are used routinely to treat Staphylococcus aureus infections. However, the emergence of methicillin-resistant S. (MRSA) renders them clinically precarious. We describe a class cinnamonitrile adjuvants that restore activity oxacillin (a penicillin member β-lactams) against MRSA. The lead were tested six important strains MRSA, one vancomycin-intermediate (VISA) strain, and linezolid-resistant strain. Five compounds out 84 total showed broad potentiation. At 8 μM...
Natural product bulgecin A potentiates the activity of β-lactam antibiotics by inhibition three lytic transglycosylases in Pseudomonas aeruginosa, which MltD is one. exhibits both endolytic and exolytic reactions turnover cell-wall peptidoglycan tolerates presence or absence stem peptides its substrates. The present study reveals structural features multimodular MltD, presenting a catalytic module four cell-wall-binding LysM modules that account for these attributes. Three X-ray structures...
Peptidoglycan is a major constituent of the bacterial cell wall. Its integrity as polymeric edifice critical for survival and, such, it preeminent target antibiotics. The peptidoglycan dynamic crosslinked polymer that undergoes constant biosynthesis and turnover. soluble lytic transglycosylase (Slt) Pseudomonas aeruginosa periplasmic enzyme involved in this Using amber-codon-suppression methodology live bacteria, we incorporated fluorescent chromophore into structure Slt. Fluorescent...
Heterologous overexpression of foreign proteins in Escherichia coli often leads to insoluble aggregates misfolded inactive proteins, so-called inclusion bodies. To solve this problem use chaperones or vitro refolding procedures are the means choice. These methods time consuming and cost intensive, due additional purification steps get rid chaperons process itself. We describe an easy lab-scale method avoid formation The systematically combines co-solvents, usually applied for stabilization...
Abstract Muropeptides are a group of bacterial natural products generated from the cell wall in course its turnover. These compounds cell‐wall recycling intermediates and also involved signaling within bacterium. However, identity these molecules remains elusive. The identification characterization 20 muropeptides Pseudomonas aeruginosa is described. least abundant metabolites present at 100 most 55,000 per Analysis under conditions induction resistance to β‐lactam antibiotic identified two...
Clostridioides difficile is a leading health threat. This pathogen initiates intestinal infections during gut microbiota dysbiosis caused by oral administration of antibiotics. C. difficult to eradicate due its ability form spores, which are not susceptible To address the urgent need for treating recurrent infection, antibiotics that selectively target over common needed. We herein describe class picolinamide antibacterials show potent and selective activity against difficile. The...
In Abbildung 1 B dieser Zuschrift wurden die Produkte der Reaktionen von 2 e mit PBP4 und AmpDh3 verwechselt. Die Reaktion führt zu d, a, wie in korrigierten unten gezeigt. Haupttext Abbildungslegende ergeben sich dadurch keine Änderungen. A) Chemical structures of detected muropeptides. B) The chemoenzymatic syntheses six