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

被引:53
作者
Sorrentino, Flavia [1 ,2 ]
Gonzalez del Rio, Ruben [2 ]
Zheng, Xingji [1 ]
Presa Matilla, Jesus [2 ]
Torres Gomez, Pedro [2 ]
Martinez Hoyos, Maria [2 ]
Perez Herran, Maria Esther [2 ]
Mendoza Losana, Alfonso [2 ]
Av-Gay, Yossef [1 ]
机构
[1] Univ British Columbia, Fac Med, Dept Med, Div Infect Dis, Vancouver, BC, Canada
[2] GSK, Dis Dev World, Madrid, Spain
关键词
DRUG SUSCEPTIBILITY; PYRAZINAMIDE; DISCOVERY; VIRULENCE; MEMBRANE; MODEL; ACID;
D O I
10.1128/AAC.01920-15
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
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.
引用
收藏
页码:640 / 645
页数:6
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