High-Content Screening of Raw Actinomycete Extracts for the Identification of Antituberculosis Activities

Abstract

The feasibility and relevance of screening a library of raw actinomycete extracts (ECUM library) for the identification of antituberculosis activities was assessed on 11,088 extracts using a multiple-screening approach. Each extract was first tested at two concentrations against noninfected macrophages as a control, then against Mycobacterium tuberculosis growing in broth medium as well as infecting murine macrophages. The screening results indicated a library of good quality with an apparent low proportion of cytotoxic extracts. A correlation was found between both bacterial assays, but the intracellular assay showed limitations due to low rates of cell survival. Several extracts of interest were highlighted by this multiple screening. A focus on the strain producing the two most effective revealed similarities with known producers of active molecules, suggesting the possibility of selecting relevant extracts using this strategy.