A high-throughput whole cell screen to identify inhibitors of Mycobacterium tuberculosis
| Autor: | David M. Roberts, Mai A. Bailey, Allen Casey, Tanya Parish, Anuradha Kumar, Juliane Ollinger |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
Luminescence
Information Theory Antitubercular Agents 01 natural sciences law.invention chemistry.chemical_compound law Drug Discovery Medicine and Health Sciences 0303 health sciences Multidisciplinary Physics Electromagnetic Radiation Tuberculosis Drug Discovery Actinobacteria Physical Sciences Recombinant DNA Engineering and Technology Medicine Growth inhibition Rifampin Research Article Computer and Information Sciences Tuberculosis Drug Research and Development Phenotypic screening High-throughput screening Science Virulence Library Screening Microbial Sensitivity Tests Biology Research and Analysis Methods Microbiology Fluorescence Mycobacterium tuberculosis 03 medical and health sciences Drug Development Microbial Control medicine Molecular Biology Techniques Signal to Noise Ratio Molecular Biology 030304 developmental biology Pharmacology Molecular Biology Assays and Analysis Techniques Bacteria Background Signal Noise Organisms Biology and Life Sciences Reproducibility of Results biology.organism_classification medicine.disease Virology High Throughput Screening In vitro 0104 chemical sciences High-Throughput Screening Assays 010404 medicinal & biomolecular chemistry Luminescent Proteins chemistry Antibiotic Resistance Signal Processing Antimicrobial Resistance Whole cell |
| Zdroj: | PLoS ONE, Vol 14, Iss 1, p e0205479 (2019) PLoS ONE |
| ISSN: | 1932-6203 |
| Popis: | Tuberculosis is a disease of global importance for which novel drugs are urgently required. We developed a whole-cell phenotypic screen which can be used to identify inhibitors of Mycobacterium tuberculosis growth. We used recombinant strains of virulent M. tuberculosis which express far-red fluorescent reporters and used fluorescence to monitor growth in vitro. We optimized our high throughput assays using both 96-well and 384-well plates; both formats gave assays which met stringent reproducibility and robustness tests. We screened a compound set of 1105 chemically diverse compounds previously shown to be active against M. tuberculosis and identified primary hits which showed ≥ 90% growth inhibition. We ranked hits and identified three chemical classes of interest – the phenoxyalkylbenzamidazoles, the benzothiophene 1–1 dioxides, and the piperidinamines. These new compound classes may serve as starting points for the development of new series of inhibitors that prevent the growth of M. tuberculosis. This assay can be used for further screening, or could easily be adapted to other strains of M. tuberculosis. |
| Databáze: | OpenAIRE |
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