摘要：SummaryThe type VII secretion system (T7SS) ofMycobacterium tuberculosissecretes three substrate classes: Esx, Esp, and PE/PPE proteins, that play important roles in bacterial physiology and host interaction. Five subtypes of T7SS, namely ESX-1 to ESX-5, are present inM. tb. ESX-4 is the progenitor of T7SS but its function is not understood. We investigated the ESX-4 system inMycobacterium marinum. We show that ESX-4 ofM. marinumdoes not secrete its cognate substrates, EsxT and EsxU, under the conditions tested. Paradoxically, the deletion ofeccC4, an essential component of ESX-4, resulted in elevated secretion of protein substrates of ESX-1 and ESX-5. Consequently, the ΔeccC4mutant was more efficient in inducing actin cytoskeleton rearrangement, which led to enhanced phagocytosis by macrophages. Our results reveal an intimate crosstalk between the progenitor of T7SS and its more recent duplication and expansion, and provide new insight into the evolution of T7SS in mycobacteria.Graphical abstractDisplay OmittedHighlights•ESX-4 ofM. marinumdoes not constitute an active secretion system•Deletion ofeccC4of ESX-4 increases secretion of ESX-1 and ESX-5 substrates•ΔeccC4is more efficient in inducing cytoskeletal rearrangement of macrophages•Deletion ofeccC4does not affect the virulence ofM. marinumin zebrafishMolecular biology; Microbiology
