A5049354738- Bacterial biofilms and quorum sensing
- Antimicrobial Resistance in Staphylococcus
- Bacterial Genetics and Biotechnology
- Antimicrobial Peptides and Activities
- Biochemical and Structural Characterization
- Protein Structure and Dynamics
- Monoclonal and Polyclonal Antibodies Research
- Bacteriophages and microbial interactions
- Bacterial Identification and Susceptibility Testing
- RNA and protein synthesis mechanisms
- 14-3-3 protein interactions
- thermodynamics and calorimetric analyses
- Lipid Membrane Structure and Behavior
- Spectroscopy Techniques in Biomedical and Chemical Research
- Spectroscopy and Chemometric Analyses
- Infective Endocarditis Diagnosis and Management
- Regulation of Appetite and Obesity
- Antimicrobial agents and applications
- RNA Research and Splicing
- Cell Image Analysis Techniques
- interferon and immune responses
- Virus-based gene therapy research
- CRISPR and Genetic Engineering
- Supramolecular Self-Assembly in Materials
- vaccines and immunoinformatics approaches
KU Leuven
2012-2025
VIB-KU Leuven Center for Brain & Disease Research
2016-2025
Recalcitrant bacterial infections can be caused by various types of dormant bacteria, including persisters and viable but nonculturable (VBNC) cells. Despite their clinical importance, we know fairly little about dormancy development recovery. Previously, established a correlation between protein aggregation in Escherichia coli. Here, present further support for direct relationship both. Our experiments demonstrate that aggregates progressively sequester proteins involved energy production,...
While persistence and the viable but nonculturable (VBNC) state are currently investigated in isolation, our results strongly indicate that these phenotypes represent different stages of same dormancy program they should therefore be studied within conceptual framework. Moreover, we show here for first time dynamics protein aggregation perfectly match onset further development bacterial dormant linked to aggregation.
Most human proteins possess amyloidogenic segments, but only about 30 are associated with amyloid-associated pathologies, and it remains unclear what determines amyloid toxicity. We designed vascin, a synthetic peptide, based on an fragment of vascular endothelial growth factor receptor 2 (VEGFR2), protein that is not to amyloidosis. Vascin recapitulates key biophysical biochemical characteristics natural amyloids, penetrates cells, seeds the aggregation VEGFR2 through direct interaction....
Aggregation is a sequence-specific process, nucleated by short aggregation-prone regions (APRs) that can be exploited to induce aggregation of proteins containing the same APR. Here, we find most APRs are unique within proteome, but small minority occur in many proteins. When bacteria such frequently occurring APRs, it leads massive and lethal inclusion body formation large number Buildup bacterial resistance against these peptides slow. In addition, approach effective drug-resistant...
Abstract There is evidence that pathogenic bacteria can adapt to antiseptics upon repeated exposure. More alarming the concomitant increase in antibiotic resistance has been described for some pathogens. Unfortunately, effects of adaptation and cross-adaptation are hardly known oral pathogens, which very frequently exposed antiseptics. Therefore, this study aimed determine vitro minimum inhibitory concentrations (MICs) pathogens after exposure chlorhexidine or cetylpyridinium chloride,...
ABSTRACT The increased use of medical implants has resulted in a concomitant rise device-related infections. majority these infections are caused by Staphylococcus epidermidis biofilms. Immunoprophylaxis and immunotherapy targeting vivo -expressed, biofilm-associated, bacterial cell surface-exposed proteins promising new approaches to prevent treat biofilm-related infections, respectively. Using an silico procedure, we identified 64 that predicted be S . e pidermidis s urface exposed (Ses),...
Drug-resistant bacteria pose an urgent global health threat, necessitating the development of antibacterial compounds with novel modes action. Protein biosynthesis accounts for up to half energy expenditure bacterial cells, and consequently inhibiting efficiency or fidelity ribosome is a major target existing antibiotics. Here, we describe alternative mode action that affects same process: allowing translation proceed but causing co-translational aggregation nascent peptidic chain. We show...
Abstract The human ubiquitous protein cystinosin is responsible for transporting the disulphide amino acid cystine from lysosomal compartment into cytosol. In humans, Pathogenic mutations of CTNS lead to defective function, intralysosomal accumulation and development cystinosis. Kidneys are initially affected with generalized proximal tubular dysfunction (renal Fanconi syndrome), then disease rapidly affects glomeruli progresses towards end stage renal failure multiple organ dysfunction....
Abstract Human amyloids have been shown to interact with viruses and interfere viral replication. Based on this observation, we employed a synthetic biology approach in which engineered virus-specific against influenza A Zika proteins. Each amyloid shares homologous aggregation-prone fragment specific target protein. For demonstrate that designer PB2 accumulates A-infected tissue vivo. Moreover, acts specifically its common polymorphisms, but not B, lacks the fragment. Our model demonstrates...
Functional bacterial amyloid provides structural stability in biofilm, making it a promising target for anti-biofilm therapeutics. Fibrils formed by CsgA, the major component E. coli are extremely robust and can withstand very harsh conditions. Like other functional amyloids, CsgA contains relatively short aggregation-prone regions (APR) which drive formation. Here, we demonstrate use of aggregation-modulating peptides to knock down protein into aggregates with low altered morphology....
Staphylococcus epidermidis is the most common cause of device-associated infections. It has been shown that active and passive immunization in an animal model against protein SesC significantly reduces S. biofilm-associated In order to elucidate its role, knock-out sesC or isolation sesC-negative mutants were attempted, however, without success. As alternative strategy, was introduced into aureus 8325-4 isogenic icaADBC srtA mutants, clinical methicillin-sensitive isolate MSSA4 MRSA BH1CC,...
Mutant KRAS is a major driver of oncogenesis in multitude cancers but remains challenging target for classical small molecule drugs, motivating the exploration alternative approaches. Here, we show that aggregation-prone regions (APRs) primary sequence oncoprotein constitute intrinsic vulnerabilities can be exploited to misfold into protein aggregates. Conveniently, this propensity present wild-type increased common oncogenic mutations at positions 12 and 13. We synthetic peptides...
There is an arms race between beta-lactam antibiotics development and co-evolving beta-lactamases, which provide resistance by breaking down rings. We have observed that certain beta-lactamases tend to aggregate, persists throughout their evolution under the selective pressure of on active sites. Interestingly, we find existing beta-lactamase site inhibitors can act as molecular chaperones, promoting proper folding these factors. Therefore, created Pept-Ins, synthetic peptides designed...
Inclusion bodies (IBs) are well-known subcellular structures in bacteria where protein aggregates collected. Various methods have probed their structure, but single-cell spectroscopy remains challenging. Atomic Force Microscopy-based Infrared Spectroscopy (AFM-IR) is a novel technology with high potential for the characterisation of biomaterials such as IBs.
Despite our extensive knowledge of the genetic regulation heat shock proteins (HSPs), evolutionary routes that allow bacteria to adaptively tune their HSP levels and corresponding proteostatic robustness have been explored less. In this report, directed evolution experiments using Escherichia coli model system unexpectedly revealed seemingly random single mutations in its tnaA gene can confer significant resistance.
Pituitary adenylate cyclase-activating polypeptide (PACAP) is an inhibitor of megakaryopoiesis and platelet function. Recently, PACAP deficiency was observed in children with nephrotic syndrome (NS), associated increased count aggregability risk thrombosis. To further study NS, we used transgenic Tg(cd41:EGFP) zebrafish GFP-labeled thrombocytes. We generated two models for congenital a morpholino injected model targeting nphs1 (nephrin), which mutated the Finnish-type NS. The second induced...
The overconsumption and inappropriate use of antibiotics is escalating antibiotic resistance development, which now one the 10 top threats to global health. Introducing with a novel mode action into clinical urgently needed address this issue. Deliberately inducing aggregation target proteins disrupting protein homeostasis in bacteria via amyloidogenic peptides, also called Pept-ins (from pept ide terferors), can be lethal shows considerable promise as strategy. However, translation clinic...
Staphylococcus epidermidis account for the majority of foreign body-related infections particularly catheter-related infections.Its ability to adhere materials and promote formation a biofilm is most important feature its pathogenicity.The presence S. surface components SesC protein essential formation.Accordingly, in addition antibiotic therapy has recently been lot attention on development vaccines against proteins.The aim this study detection phenotype isolated from respiratory catheters...
Abstract Background Inclusion bodies (IBs) are well-known subcellular structures in bacteria where protein aggregates collected. Various methods have probed their structure, but single-cell spectroscopy remains challenging. Atomic Force Microscopy-based Infrared Spectroscopy (AFM-IR) is a novel technology with high potential for the characterisation of biomaterials such as IBs. Results We present detailed investigation using AFM-IR, revealing substructure IBs and variation at level,...
Amyloid-like aggregation of proteins is induced by short amyloidogenic sequence segments within a specific protein resulting in self-assembly into β-sheets. We recently validated technology platform which synthetic amyloid peptides ("Pept-ins") containing aggregation-prone region (APR) are used to induce functional knockdown the target from APR was derived, including bacterial, viral, and mammalian cell proteins. In this work, we investigated if Pept-ins can be as vector probes for vivo...