- Yersinia bacterium, plague, ectoparasites research
- Escherichia coli research studies
- Bacterial Genetics and Biotechnology
- Bacteriophages and microbial interactions
- Vibrio bacteria research studies
- Viral gastroenteritis research and epidemiology
- Bacterial Infections and Vaccines
- Bacillus and Francisella bacterial research
- Antibiotic Resistance in Bacteria
- RNA Interference and Gene Delivery
- Plant-based Medicinal Research
- Antimicrobial Peptides and Activities
- Monoclonal and Polyclonal Antibodies Research
- Toxin Mechanisms and Immunotoxins
- Immune Response and Inflammation
- Chronic Lymphocytic Leukemia Research
- Advanced biosensing and bioanalysis techniques
- Lymphoma Diagnosis and Treatment
- Cell Adhesion Molecules Research
- Cerebrovascular and genetic disorders
- Barrier Structure and Function Studies
- Cellular transport and secretion
- Acne and Rosacea Treatments and Effects
- Erythrocyte Function and Pathophysiology
- Oral microbiology and periodontitis research
University of Münster
2010-2022
Institute of Molecular Biology
2021
Outer membrane vesicles (OMVs) are important tools in bacterial virulence but their role the pathogenesis of infections caused by enterohemorrhagic Escherichia coli (EHEC) O157, leading cause life-threatening hemolytic uremic syndrome, is poorly understood. Using proteomics, electron and confocal laser scanning microscopy, immunoblotting, bioassays, we investigated OMVs secreted EHEC O157 clinical isolates for factors cargoes, interactions with pathogenetically relevant human cells,...
Enterohemorrhagic Escherichia coli (EHEC) strains cause diarrhea and hemolytic uremic syndrome resulting from toxin-mediated microvascular endothelial injury. EHEC hemolysin (EHEC-Hly), a member of the RTX (repeats-in-toxin) family, is an virulence factor increasingly recognized importance. The toxin exists as free EHEC-Hly associated with outer membrane vesicles (OMVs) released by during growth. Whereas lytic towards human endothelium, biological effects OMV-associated on intestinal...
The highly virulent Escherichia coli O104:H4 that caused the large 2011 outbreak of diarrhoea and haemolytic uraemic syndrome secretes blended virulence factors enterohaemorrhagic enteroaggregative E. coli, but their secretion pathways are unknown. We demonstrate strain releases a cocktail via outer membrane vesicles (OMVs) shed during growth. OMVs contain Shiga toxin (Stx) 2a, major factor strain, Shigella enterotoxin 1, H4 flagellin, O104 lipopolysaccharide. bind to internalised by human...
Tightly controlled epithelial and endothelial barriers are a prerequisite for life as these separate multicellular organisms from their environment serve first lines of defense. Barriers between neighboring cells formed by multiple intercellular junctions including the 'apical junctional complex-AJC' with tight (TJ), adherens (AJ), desmosomes. TJ consist tetraspan transmembrane proteins like occludin, various claudins that directly control paracellular permeability, 'Junctional Adhesion...
The Gram-positive anaerobic bacterium Cutibacterium acnes is a commensal of the human skin, but also an opportunistic pathogen that contributes to pathophysiology skin disease acne vulgaris. Moreover, C. acnes, in addition other skin-colonizing bacteria such as S. epidermidis and aureus, emerging implant-associated infections. Notably, isolates exhibit marked heterogeneity can be divided into at least 6 phylotypes by multilocus sequence typing. It becoming increasingly evident biofilm...
Commonly used antimicrobials show poor cellular uptake and often have limited access to intracellular targets, resulting in low antimicrobial activity against pathogens. An efficient delivery system transport these drugs the site of action is needed. Cell-penetrating peptides (CPPs) mediate internalization biologically active molecules into cytoplasm. Here, we characterized two CPPs, α1H α2H, derived from Yersinia enterocolitica YopM effector protein. These as well Tat (trans-activator...
Abstract The small arginine-rich protein protamine condenses complete genomic DNA into the sperm head. Here, we applied its high RNA binding capacity for spontaneous electrostatic assembly of therapeutic nanoparticles decorated with tumour-cell-specific antibodies efficiently targeting siRNA. Fluorescence microscopy and DLS measurements these nanocarriers revealed formation a vesicular architecture that requires presence antibody-protamine, defined excess free SMCC-protamine, anionic siRNA...
Cell-permeable proteins, also called cell-penetrating peptides (CPPs), have the ability to cross cellular membranes, either alone or in association with bioactive cargo. We identified Yersinia protein YopM as a novel bacterial cell-permeable protein. Here, we describe of isolated recombinant enter host cells without requirement for additional factors. This autonomous translocation was confirmed several cell types, indicating that it is an intrinsic property YopM. Using truncated versions...
Abstract Background Acute myeloid leukemia (AML) is a fatal clonal hematopoietic malignancy, which results from the accumulation of several genetic aberrations in progenitor cells, with worldwide 5-year survival prognosis about 30%. Therefore, development more effective therapeutics novel mode action urgently demanded. One common mutated gene AML DNA-methyltransferase DNMT3A whose function and maintenance still unclear. To specifically target “undruggable” oncogenes, we initially invented an...
The effector protein Yersinia outer M (YopM) of enterocolitica has previously been identified and characterized as the first bacterial cell-penetrating (CPP). We found that recombinant YopM (rYopM) enters different eukaryotic cell types downregulates expression several pro-inflammatory cytokines (e.g., tumor necrosis factor-α [TNF-α]) after autonomous translocation. After infection with Y. or transfection host cells, interacts isoforms two kinases ribosomal S6 kinase (RSK) C-related (PRK)....
Abstract Cytotoxic necrotizing factors (CNFs) are bacterial single‐chain exotoxins that modulate cytokinetic/oncogenic and inflammatory processes through activation of host cell Rho GTPases. To achieve this, they secreted, bind surface receptors to induce endocytosis translocate a catalytic unit into the cytosol intoxicate cells. A three‐dimensional structure provides insight underlying mechanisms is still lacking. Here, we determined crystal full‐length Yersinia pseudotuberculosis CNF Y ....
Enteropathogenic Escherichia coli (EPEC), atypical enteropathogenic (ATEC) and enterohemorrhagic (EHEC) belong to the family of attaching effacing (A/E) pathogens. Pathogenicity is mediated by subversion host cell functions involving type III secretion system (TTSS)-dependent effector proteins. In this study, we have identified characterized a novel TTSS-dependent protein encoded at 5'-end locus enterocyte effacement (LEE) pathogenicity island (PAI) ATEC strain 3431-4/86 (O8:H(-)). Using...
Effector proteins secreted by the type 3 secretion system (T3SS) of pathogenic bacteria have been shown to precisely modulate important signaling cascades host for benefit pathogens. Among others, non-LEE encoded T3SS effector protein NleC enteropathogenic Escherichia coli (EPEC) is a Zn-dependent metalloproteinase and suppresses innate immune responses directly targeting NF-κB pathway. Many release potent bacterial toxins A-B type, which - in contrast direct cytoplasmic injection are...
The pathogenesis of enteropathogenic Escherichia coli (EPEC) is characterized by the type III secretion system-dependent exploitation target cells that results in attaching and effacing (A/E) lesions, actin rearrangements pedestal formation. This pathology mediated effector proteins which are translocated system into host cell such as intimin receptor (Tir) several E. secreted (Esp). Secretion virulence EPEC tightly regulated. In response to Ca2+, Esp drastically reduced, whereas Tir...
ABSTRACT Alongside the well-characterized enterohemorrhagic Escherichia coli (EHEC) O157:H7, serogroup O157 comprises sorbitol-fermenting typical and atypical enteropathogenic E. (EPEC/aEPEC) strains that carry intimin-encoding gene eae but not Shiga toxin-encoding genes ( stx ). Since little is known about these pathogens, we characterized 30 clinical isolates from patients with hemolytic uremic syndrome (HUS) or uncomplicated diarrhea respect to their flagellin fliC ) type multilocus...