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- W2057372923 endingPage "e87834" @default.
- W2057372923 startingPage "e87834" @default.
- W2057372923 abstract "Tuberculosis is considered to be one of the world’s deadliest disease with 2 million deaths each year. The need for new antitubercular drugs is further exacerbated by the emergence of drug-resistance strains. Despite multiple recent efforts, the majority of the hits discovered by traditional target-based screening showed low efficiency in vivo. Therefore, there is heightened demand for whole-cell based approaches directly using host-pathogen systems. The phenotypic host-pathogen assay described here is based on the monitoring of GFP-expressing Mycobacterium marinum during infection of the amoeba Acanthamoeba castellanii. The assay showed straight-forward medium-throughput scalability, robustness and ease of manipulation, demonstrating its qualities as an efficient compound screening system. Validation with a series of known antitubercular compounds highlighted the advantages of the assay in comparison to previously published macrophage-Mycobacterium tuberculosis-based screening systems. Combination with secondary growth assays based on either GFP-expressing D. discoideum or M. marinum allowed us to further fine-tune compound characterization by distinguishing and quantifying growth inhibition, cytotoxic properties and antibiotic activities of the compounds. The simple and relatively low cost system described here is most suitable to detect anti-infective compounds, whether they present antibiotic activities or not, in which case they might exert anti-virulence or host defense boosting activities, both of which are largely overlooked by classical screening approaches." @default.
- W2057372923 created "2016-06-24" @default.
- W2057372923 creator A5009066976 @default.
- W2057372923 creator A5017012001 @default.
- W2057372923 creator A5017167988 @default.
- W2057372923 creator A5021979769 @default.
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- W2057372923 creator A5061765661 @default.
- W2057372923 creator A5063733053 @default.
- W2057372923 creator A5074290277 @default.
- W2057372923 creator A5077045916 @default.
- W2057372923 date "2014-01-31" @default.
- W2057372923 modified "2023-10-02" @default.
- W2057372923 title "Establishment and Validation of Whole-Cell Based Fluorescence Assays to Identify Anti-Mycobacterial Compounds Using the Acanthamoeba castellanii - Mycobacterium marinum Host-Pathogen System" @default.
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