In this study, the authors describe a multistep pathway for targeting Mycobacterium tuberculosis for autophagy. The M. tuberculosis type VII secretion system ESX1 was shown to permeabilize bacterium-containing phagosomes in bone marrow-derived macrophages. This permeabilization allows bacterial DNA to be recognized by the cytosolic sensor STING (stimulator of interferon genes). STING is required for the marking of bacteria with ubiquitin, which initiates the ubiquitin-mediated autophagy pathway through the recruitment of autophagy components, such as LC3, to the bacteria. The targeting of autophagy components to M. tuberculosis requires the ubiquitin-binding autophagy receptors p62 (also known as SQSTM1) and NDP52, together with the kinase TBK1, and delivers the bacilli to autophagosomes. Autophagosomes then fuse with lysosomes to create autophagolysosomes, and this results in bacterial killing. Finally, autophagy was shown to be required for effective control of M. tuberculosis infection in vivo.