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- Research Expertise:My research focuses on: (1) Investigating the impact of antibiotic use on human pathogens and commensal flora utilizing genetic, genomic and microbiomic approaches: Utilizing the oro-pharyngeal streptococcal flora in healthy and infected individuals as a model, we have demonstrated that antibiotic use is the single most important driver of antibiotic-resistance in vivo, that antibiotics belonging to the same class can differ widely in resistance gene selection, and that differences in predominance of certain resistance genes in geographically distinct areas might be linked to the preferential use of specific antibiotic subclasses. Now, we are studying changes in the resistome and in composition of the intestinal flora of patients in intensive care units undergoing selective oral or digestive decontamination utilizing metagenomic and functional genomic approaches. (2) Mechanisms of antibiotic resistance in pathogenic bacteria: The main focus is on investigating 'old' antibiotics that have been reintroduced into clinical practice and whose resistance mechanisms are not yet known such as colistin, nitrofurantoin and fosfomycin. Both clinical, patient derived strains as well as in vitro passaged strains undergo strain typing, whole genome sequencing, resistance stability studies and fitness cost assessments to understand emergence of the resistance mechanisms as well as their fate in the community. (3) Biofilms: As an increasing number of critical infections and their persistence are being linked to biofilm formation, investigations on bacterial isolates, while indispensable for species identification and metabolic and genetic studies, cannot give insights on disease pathogenesis. We have primarily chosen to study device-related infections, such as ventilator-associated pneumonia and catheter infections, where biofilm formation is most relevant, aiming to characterize mechanisms underlying biofilm formation and the microbial interactions in a biofilm both in vitro and in vivo. Several in vitro biofilm models, both static and dynamic shear-flow, have been set up in our laboratory for these studies. In vivo biofilms obtained from explanted catheters are being analysed using culture-dependent and -independent approaches as well as by confocal laser scanning microscopy.
- Keywords:MOLECULAR BIOLOGY, GENOME ANALYSIS, BIOFILMS, ANTIBIOTIC RESISTANCE, ANTIBIOTIC RESISTANT BACTERIA (ARB), MICROBIAL GENETICS, Biomedical sciences (incl. biochemistry)
- Disciplines:Genetics, Laboratory medicine, Palliative care and end-of-life care, Regenerative medicine, Other basic sciences, Other clinical sciences, Other health sciences, Nursing, Other paramedical sciences, Other translational sciences, Other medical and health sciences
- Research techniques:In vitro biofilm models Static high throughput models Dynamic shear-flow model (Bioflux 200 system and the Copenhagen model) Whole genome mapping (Argus Whole Genome Mapper, Opgen Inc.) Whole genome sequencing 16S metagenome profiling Functional genomics Gene knock-out and site-directed mutagenesis Transcriptomics (microarray-based and RNASeq) Fluorescence microscopy Confocal microscopy Phenotypic testing for antimicrobial susceptibility (Disc diffusion, MIC testing) Genotypic testing for antimicrobial susceptibility (PCR, Real-time PCR) Bacterial speciation on MALDI-TOF
- Users of research expertise:Pharmaceutical companies Small and medium enterprises Academic groups