The expanding universe of contractile injection systems in bacteria

Contractile injection systems (CISs) are phage tail–like machineries found in a wide range of bacteria. They are often deployed by bacteria to translocate effectors into the extracellular space or into target cells. CISs are classified into intracellular type VI secretion systems (T6SSs) and extracellular CIS (eCISs). eCISs are assembled in cytoplasm and released into the extracellular milieu upon cell lysis, while T6SSs are the secretion systems widespread among Gram-negative bacteria and actively translocate effectors into the environment or into the adjacent cell, without lysis of T6SS–producing cells. Recently, several noncanonical CISs that exhibit distinct characteristics have been discovered. This review will provide an overview on these noncanonical CISs and their unique features, as well as new advances in reprogramming CISs for therapeutic protein delivery.