The extracellular contractile injection system (eCIS) is a cell-free protein delivery system that is prevalent in bacteria and archaea but its biological function is poorly understood. The eCIS particle resembles the contractile tail of a T4 bacteriophage and is mostly encoded by an operon of 15-28 genes. This protein complex is 110-120 nm long and includes a baseplate, a sheathed hollow tube that has a needle-like tip (spike) on one side and a cap on the other side, and tail fibers that likely serve to adhere to target cells.

eCIS contraction propels the tube out of the sheath, likely enabling the sharp tip to perforate the target cell membrane. In addition to the structural proteins, eCIS particles are associated with effectors, which are proteins that are injected by the particle into target cells upon contraction. These effectors are usually encoded within the 3’ end of the operon. The studied effectors have enzymatic activities in the target cell, most of which lead to cell toxicity. eCIS shares structural similarity with other contractile nanoweapons such as type VI secretion system (T6SS) and R-type pyocins but differs from these by being extracellular and by injecting effectors into the target cell, respectively. Despite the prevalence of eCISs across the microbial world, only a few eCIS loci have been experimentally studied.