Identification and structure of an extracellular contractile injection system from a marine bacterium

February 16, 2022

In their study of a putative CIS gene cluster in the marine bacterium Algoriphagus machipongonensis, NOMIS researcher Martin Pilhofer and colleagues have revealed several features that are required for assembly, cargo loading and function. Their findings were published in Nature Microbiology.


Contractile injection systems (CISs) are phage tail-like nanomachines, mediating bacterial cell–cell interactions as either type VI secretion systems (T6SSs) or extracellular CISs (eCISs). Bioinformatic studies uncovered a phylogenetic group of hundreds of putative CIS gene clusters that are highly diverse and widespread; however, only four systems have been characterized. Here we studied a putative CIS gene cluster in the marine bacterium Algoriphagus machipongonensis. Using an integrative approach, we show that the system is compatible with an eCIS mode of action. Our cryo-electron microscopy structure revealed several features that differ from those seen in other CISs: a ‘cap adaptor’ located at the distal end, a ‘plug’ exposed to the tube lumen, and a ‘cage’ formed by massive extensions of the baseplate. These elements are conserved in other CISs, and our genetic tools identified that they are required for assembly, cargo loading and function. Furthermore, our atomic model highlights specific evolutionary hotspots and will serve as a framework for understanding and re−engineering CISs.


In most ecological settings, bacteria do not exist as isolated cells, but interact with other organisms. These cell–cell interactions are often mediated by macromolecular machines that translocate effector proteins into the medium or directly into a target cell. Bacterial contractile injection systems (CISs) mediate cell–cell interactions between bacterial and eukaryotic cells and often confer competitive advantage in different environmental niches. CISs are macromolecular injection devices with an overall structure that is homologous to the contractile tails of bacteriophages. Their conserved modules include an inner tube, a contractile sheath and a baseplate complex. For firing of the extended apparatus, the baseplate undergoes a conformational change and triggers sheath contraction, which in turn causes the inner tube to be expelled and injected into a target.

On the basis of distinct modes of action, bacterial CISs are classified into extracellular CISs (eCISs) and type VI secretion systems (T6SSs). eCISs resemble headless phage particles that are assembled in the bacterial cytoplasm and then released into the medium upon cell lysis. Upon binding to a target cell via tail fibres, eCISs contract and puncture the target’s cell envelope10. By contrast, T6SSs remain intracellular and are anchored to the inner membrane, injecting effectors by a cell–cell contact-dependent mechanism.

Continue reading this Nature Microbiology publication: Identification and structure of an extracellular contractile injection system from the marine bacterium Algoriphagus machipongonensis