In vivo chemical-genetic interactions of Mycobacterium tuberculosis

Mice were infected with a library of ATC/doxycycline-inducible M. tuberculosis degron library targeting essential proteins, followed by 2 weeks of treatment with an optimized dose of Isoniazid, Rifampicin, Pyrazinamide, or a combination of the three plus Ethambutol (HRZE). At the end of the treatment period, bacteria were recovered from the lungs, outgrown in 7H10, followed by DNA extraction and Illumina deep sequencing of the unique barcode junctions.