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00925njm 22002777a 4500 dc Rivera Calzada, Angel author Famelis, Nikolaos author Llorca Blanco, Oscar Antonio author Geibel, Sebastian author 2021-09 Type VII secretion systems (T7SSs) have a key role in the secretion of effector proteins in non-pathogenic mycobacteria and pathogenic mycobacteria such as Mycobacterium tuberculosis, the main causative agent of tuberculosis. Tuberculosis-causing mycobacteria, still accounting for 1.4 million deaths annually, rely on paralogous T7SSs to survive in the host and efficiently evade its immune response. Although it is still unknown how effector proteins of T7SSs cross the outer membrane of the diderm mycobacterial cell envelope, recent advances in the structural characterization of these secretion systems have revealed the intricate network of interactions of conserved components in the plasma membrane. This structural information, added to recent advances in the molecular biology and regulation of mycobacterial T7SSs as well as progress in our understanding of their secreted effector proteins, is shedding light on the inner working of the T7SS machinery. In this Review, we highlight the implications of these studies and the derived transport models, which provide new scenarios for targeting the deathly human pathogen M. tuberculosis. Nat Rev Microbiol . 2021 Sep;19(9):567-584. Nature Reviews Microbiology 34040228 https://hdl.handle.net/20.500.12105/27230 Type VII secretion systems: structure, functions and transport models.