Mycobacterium tuberculosis, the causative agent of tuberculosis, remains a leading cause of death by infectious diseases globally. One of the hallmarks of tuberculosis is the ability of the bacteria to cause persistent infection by evading the host adaptive immune response. The Tischler lab seeks to understand the bacterial factors that enable M. tuberculosis to persist. They use a combination of bacterial genetics and a mouse model of tuberculosis infection to identify and characterize these persistence mechanisms. They conducted high-throughput genetic screens using Tn-seq technology to identify novel mechanisms of immune evasion in mice as well as mechanisms that enable the bacteria to tolerate treatment with antibiotics, and to determine whether certain genes annotated as "essential" in vitro for growth and persistence can be found in infected mice. Current work focuses on the M. tuberculosis Type VII specialized protein secretion system ESX-5 including regulators that control expression and activity of this system, identifying protein substrates of the system and determining the function of ESX-5 itself and secreted protein effectors in M. tuberculosis pathogenesis.