Type VII secretion systems (T7SSs) are poorly understood protein export apparatuses found in mycobacteria and many species of Gram‐positive bacteria. To date, this pathway has predominantly been studied in Mycobacterium tuberculosis, where it has been shown to play an essential role in virulence; however, much less studied is an evolutionarily divergent subfamily of T7SSs referred to as the T7SSb. The T7SSb is found in the major Gram‐positive phylum Firmicutes where it was recently shown to target both eukaryotic and prokaryotic cells suggesting a dual role for this pathway in host‐microbe and microbe‐microbe interactions. In this review, we compare the current understanding of the molecular architectures and substrate repertoires of the well‐studied mycobacterial T7SSa systems to that of recently characterized T7SSb pathways and highlight how these differences may explain the observed biological functions of this understudied protein export machine.
Note: Hiu‐Ki R. Tran was a undergraduate thesis student in our lab 2019-2020 and performed analysis of the type VII secretion system, but wrote this review paper independently with colleagues in the Whitney lab – well done Rachel!