T6SSs

The Type VI secretion system (T6SS) is a protein secretion apparatus used by many Gram-negative bacteria to translocate toxins into neighboring cells or host organisms. Its architecture is phage-like, featuring a contractile sheath surrounding an inner tube built from Hcp subunits, capped by a spike composed of VgrG and often PAAR proteins. A baseplate and membrane complex dock the apparatus to the cell envelope, and an ATPase such as ClpV powers contraction and recycling.

Activation drives rapid contraction of the sheath, propelling the tube and spike through the envelope and delivering effector proteins. Some effectors are injected with the tube, while others associate with the spike. Immunity proteins adjacent to effector genes protect the secreting cell from its own toxins.

T6SSs participate in interbacterial competition and, in some species, virulence against eukaryotic hosts. They can target rival bacteria, fungi, or host cells depending on the effector repertoire. Effectors show broad activities, including nucleases, lipases, peptidoglycan hydrolases, and membrane-disrupting toxins. The system is often regulated by environmental cues, population density, and direct cell contact, and many bacteria harbor multiple T6SS clusters with distinct regulation and effector sets.

Distribution and significance: T6SSs are widespread among Gram-negative bacteria and contribute to ecological fitness, niche establishment, and pathogenic potential. Their modular architecture and mobility genes facilitate horizontal transfer and rapid diversification of effectors. Research on T6SSs informs understanding of bacterial interactions and is a focus for developing antimicrobial strategies and biotechnological applications.