A5063293606- Tuberculosis Research and Epidemiology
- Mycobacterium research and diagnosis
- Biosimilars and Bioanalytical Methods
- Evolution and Genetic Dynamics
- Biochemical and Molecular Research
- Pneumocystis jirovecii pneumonia detection and treatment
- Cancer therapeutics and mechanisms
- Gut microbiota and health
- Genomics and Phylogenetic Studies
- Antibiotics Pharmacokinetics and Efficacy
- Pharmacological Effects of Natural Compounds
- Antibiotic Resistance in Bacteria
Research Center Borstel - Leibniz Lung Center
2020-2025
German Center for Infection Research
2024
Bedaquiline is a core drug for the treatment of multidrug-resistant tuberculosis; however, understanding resistance mechanisms poor, which hampering rapid molecular diagnostics. Some bedaquiline-resistant mutants are also cross-resistant to clofazimine. To decipher bedaquiline and clofazimine determinants, we combined experimental evolution, protein modelling, genome sequencing, phenotypic data.
Drug-resistant Mycobacterium tuberculosis (Mtb) remains a major public health concern requiring complementary approaches to standard anti-tuberculous regimens. Anti-virulence molecules or compounds that enhance the activity of antimicrobial prodrugs are promising alternatives conventional antibiotics. Exploiting host cell-based drug discovery, we identified an oxadiazole compound (S3) blocks ESX-1 secretion system, virulence factor Mtb. S3-treated mycobacteria showed impaired intracellular...
Abstract Bedaquiline (BDQ) and clofazimine (CFZ) are core drugs for treatment of multidrug resistant tuberculosis (MDR-TB), however, our understanding the resistance mechanisms these is sparse which hampering rapid molecular diagnostics. To address this, we employed a unique approach using experimental evolution, protein modelling, genome sequencing, minimum inhibitory concentration data combined with genomes from global strain collection over 14,151 Mycobacterium complex isolates an...
Here, we present a protocol to perform time-kill assay (TKA) quantify bacterial burden at multiple time points using colony-forming units and most probable number readouts simultaneously. We describe steps for preparing inoculum, experimental conditions, sampling counts. then detail procedures quantification analysis. TKAs provide longitudinal data reflecting the dynamics of antibiotic effect over against planktonic culture concentration-effect relationship. For complete details on use...
Global health is threatened by the rise of antibiotic resistance. Bacteria Mycobacterium tuberculosis complex (Mtbc) are a major contributor to this crisis, with about 450,000 new multidrug resistant (MDR-TB) cases per year. This study investigates resistance evolution, through defining mutant selection window (MSW) for important MDR-TB treatment drugs moxifloxacin and bedaquiline. We employed combination long-term in vitro experiments supplemented mathematical modelling that combined...
Tuberculosis (TB) is the historical leading cause of death by a single infectious agent. The European Regimen Accelerator for (ERA4TB) public-private partnership 30+ institutions with objective to progress new anti-TB regimens into clinic. Thus, robust and replicable results across independent laboratories are essential reliable interpretation treatment efficacy. A standardization workgroup unified in vitro protocols data reporting templates. Time-kill assays provide input pharmacometric...
Preexisting and newly emerging resistant pathogen subpopulations (heteroresistance) are potential risk factors for treatment failure of multi/extensively drug (MDR/XDR) tuberculosis (TB). Intrapatient evolutionary dynamics Mycobacterium complex (Mtbc) strains their implications on outcomes still not completely understood. To elucidate how Mtbc escape therapy, we analyzed 13 serial isolates from a German patient by whole-genome sequencing. Sequencing data were compared with phenotypic...
Tuberculosis (TB) is the deadliest infectious disease after COVID-19. The European Regimen Accelerator for (ERA4TB) a public-private partnership of more than 30 institutions with objective to progress new anti-TB regimens into clinic. Thus, robust and replicable results across independent laboratories are essential reliable interpretation treatment efficacy. Time-kill assays provide input data pharmacometric model informed translation single agents activity from in vitro vivo An ERA4TB...