a high-throughput screen for tuberculosis progression一个高通量筛选结核病恶化.pdfVIP

A High-Throughput Screen for Tuberculosis Progression 1,3 . 2. 3 4 Ralph Carvalho * , Jan de Sonneville , Oliver W. Stockhammer , Nigel D. L. Savage , Wouter J. 3 4 1 3 3 Veneman , Tom H. M. Ottenhoff , Ron P. Dirks , Annemarie H. Meijer , Herman P. Spaink 1 ZF-screens B.V., Leiden, The Netherlands, 2 Institute of Chemistry, Leiden University, Leiden, The Netherlands, 3 Institute of Biology, Leiden University, Leiden, The Netherlands, 4 Department of Immunohematology and Blood Transfusion, Leiden University Medical Centre, Leiden, The Netherlands Abstract One-third of the world population is infected with Mycobacterium tuberculosis and multi-drug resistant strains are rapidly evolving. The noticeable absence of a whole organism high-throughput screening system for studying the progression of tuberculosis is fast becoming the bottleneck in tuberculosis research. We successfully developed such a system using the zebrafish Mycobacterium marinum infection model, which is a well-characterized model for tuberculosis progression with biomedical significance, mimicking hallmarks of human tuberculosis pathology. Importantly, we demonstrate the suitability of our system to directly study M. tuberculosis, showing for the first time that the human pathogen can propagate in this vertebrate model, resulting in similar early disease symptoms to those observed upon M. marinum infection. Our system is capable of screening for disease progression via robotic yolk injection of early embryos and visual flow screening of late- stage larvae. We also show that this system can