Mycobacterium goes yeast: Target deconvolution of anti-tuberculosis drugs can be a very challenging task. Here we report a yeast 3-hybrid system that allows promising small molecules to be screened for protein targets of a pathogen in nontoxic yeast cells. The system employs libraries of randomly fragmented bacterial DNA and offers a technically simple alternative approach for target identification. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.