A5012511410- Tuberculosis Research and Epidemiology
- Cancer therapeutics and mechanisms
- Mycobacterium research and diagnosis
- Immune cells in cancer
- Receptor Mechanisms and Signaling
- Diagnosis and treatment of tuberculosis
- RNA and protein synthesis mechanisms
- Immune Response and Inflammation
- Biochemical and Molecular Research
- Antibiotic Resistance in Bacteria
- Zebrafish Biomedical Research Applications
- vaccines and immunoinformatics approaches
Amsterdam University Medical Centers
2021-2024
Amsterdam UMC Location Vrije Universiteit Amsterdam
2024
Vrije Universiteit Amsterdam
2021-2023
Abstract The rise of multidrug-resistant bacteria underlines the need for innovative treatments, yet introduction new drugs has stagnated despite numerous antimicrobial discoveries. A major hurdle is a poor correlation between promising in vitro data and vivo efficacy animal models, which essential clinical development. Early testing hindered by expense complexity existing models. Therefore, there pressing cost-effective, rapid preclinical models with high translational value. To overcome...
The ESX-5 secretion system is essential for the viability and virulence of slow-growing pathogenic mycobacterial species. In this study, we identified a 1,2,4-oxadiazole derivative as putative effector system. We confirmed that several newly synthesized derivatives inhibited ESX-5-dependent active lipase LipY by Mycobacterium marinum (M. marinum). Despite reduced activity, did not observe defect in itself. Moreover, found other substrates, especially high molecular-weight PE_PGRS MMAR_5294,...
ABSTRACT Finding new anti-tuberculosis compounds with convincing in vivo activity is an ongoing global challenge to fight the emergence of multidrug-resistant Mycobacterium tuberculosis isolates. In this study, we exploited medium-throughput capabilities zebrafish embryo infection model marinum as a surrogate for M. tuberculosis. Using representative set clinically established drugs, demonstrate that could be predictive and selective antibiotics can administered orally. We further used...
Developing effective tuberculosis drugs is hindered by mycobacteria’s intrinsic antibiotic resistance because of their impermeable cell envelope. Using benzothiazole compounds, we aimed to increase mycobacterial envelope permeability and weaken the defenses Mycobacterium marinum , serving as a model for . Initial hit, BT-08, significantly boosted ethidium bromide uptake, indicating enhanced membrane permeability. It also demonstrated efficacy in M. –zebrafish embryo infection -infected...
Screening strategies for antituberculosis compounds using Mycobacterium tuberculosis are time consuming and require biosafety level 3 (BSL3) facilities, which makes the development of high-throughput assays difficult expensive. marinum , a close genetic relative M. possesses several advantages as suitable model drug screening. However, despite high similarity, there some obvious differences in susceptibility to drugs between these two species, especially prodrugs ethionamide isoniazid.