Development of an Intracellular Screen for New Compounds Able To Inhibit Mycobacterium tuberculosis Growth in Human Macrophages

Here we describe the development and validation of an intracellular high-throughput screening assay for finding new antituberculosis compounds active in human macrophages. The assay consists of a luciferase-based primary identification assay, followed by a green fluorescent protein-based secondary p...

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Bibliographic Details
Published in:Antimicrobial agents and chemotherapy 2016-01, Vol.60 (1), p.640-645
Main Authors: Sorrentino, Flavia, Gonzalez del Rio, Ruben, Zheng, Xingji, Presa Matilla, Jesus, Torres Gomez, Pedro, Martinez Hoyos, Maria, Perez Herran, Maria Esther, Mendoza Losana, Alfonso, Av-Gay, Yossef
Format: Article
Language:English
Subjects:
Antitubercular Agents
Antitubercular Agents - chemistry
Antitubercular Agents - pharmacology
Cell Line
Experimental Therapeutics
Gene Expression
Genes, Reporter
Green Fluorescent Proteins - genetics
Green Fluorescent Proteins - metabolism
Hep G2 Cells
High-Throughput Screening Assays
Humans
Luciferases - genetics
Luciferases - metabolism
Macrophages
Macrophages - drug effects
Macrophages - microbiology
Microbial Sensitivity Tests
Mycobacterium tuberculosis
Mycobacterium tuberculosis - drug effects
Mycobacterium tuberculosis - growth & development
Structure-Activity Relationship
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Summary:Here we describe the development and validation of an intracellular high-throughput screening assay for finding new antituberculosis compounds active in human macrophages. The assay consists of a luciferase-based primary identification assay, followed by a green fluorescent protein-based secondary profiling assay. Standard tuberculosis drugs and 158 previously recognized active antimycobacterial compounds were used to evaluate assay robustness. Data show that the assay developed is a short and valuable tool for the discovery of new antimycobacterial compounds.
ISSN:0066-4804
1098-6596
DOI:10.1128/AAC.01920-15