title: High-content imaging of Mycobacterium tuberculosis-infected macrophages: an in vitro model for tuberculosis drug discovery.
abstract: Macrophages are reservoirs for replicating mycobacterium during tuberculosis (TB) infections. In this study, small molecules to be developed as anti-tubercular treatments were investigated for their ability to kill intracellular bacteria in in vitro macrophage models. High-content imaging technologies offer a high-throughput method to quantify a drug's ability to inhibit Mycobacterium tuberculosis intracellular invasion and multiplication in host cells. Dedicated image analysis enables the automated quantification of infected macrophages, and compounds that inhibit mycobacteria proliferation can be tested using this method. Furthermore, the implementation of the assay in 384-well microtiter plates combined with automated image acquisition and analysis allows large-scale screening of compound libraries in M. tuberculosis-infected macrophages. Here we describe a high-throughput and high-content workflow and detail its utility for the development of new TB drugs.
authors.affiliation: Institut Pasteur Korea, Screening Technologies & Pharmacology, Sampyeong-dong 696, Bundang-gu, Seongnam-si, Gyeonggi-do, Korea 463-400, Korea.
authors.forename: Thierry
authors.initials: T
authors.lastname: Christophe
authors.forename: Fanny
authors.initials: F
authors.lastname: Ewann
authors.forename: Hee Kyoung
authors.initials: HK
authors.lastname: Jeon
authors.forename: Jonathan
authors.initials: J
authors.lastname: Cechetto
authors.forename: Priscille
authors.initials: P
authors.lastname: Brodin
mesh_terms: D000818:Animals; D000995:Antitubercular Agents / Q000494:pharmacology*; D002460:Cell Line; D055808:Drug Discovery / Q000379:methods*; D006801:Humans; D007091:Image Processing, Computer-Assisted / Q000379:methods*; D008264:Macrophages / Q000382:microbiology* / Q000648:ultrastructure*; D009169:Mycobacterium tuberculosis / Q000187:drug effects* / Q000302:isolation & purification; D054852:Small Molecule Libraries / Q000494:pharmacology; D014376:Tuberculosis / Q000188:drug therapy* / Q000382:microbiology
chemical_list: D000995:Antitubercular Agents; D054852:Small Molecule Libraries