a, The bacteriophage T4 binds to the surface of a target bacterium with its tail fibres and baseplate, causing a conformational change in the outer-tube proteins and so outer-tube contraction. Consequently, the rigid inner tube is forced through the outer membrane (OM) of the bacterium. The peptidoglycan-degrading domains of the tip proteins then allow penetration through the periplasmic peptidoglycan lattice, and finally interaction with the cytoplasmic membrane (CM) initiates translocation of viral DNA into the cytoplasm. b, The bacterial type VI secretion system (T6SS) is proposed to function similarly, because several proteins in the two systems are structurally similar (shown in the same colours)1,6,7. Mougous and colleagues2 show that two T6SS effectors of Pseudomonas aeruginosa (Tse1 and Tse3) degrade peptidoglycan; their associated immunity proteins (Tsi1 and Tsi3) are protective only when located in the periplasm. These data support the model (shown) that T6SS delivers proteins across only one membrane, and that secreted proteins are delivered from the cytoplasm of the injecting cell into the periplasm of the target cell without entering the periplasm of the injecting cell. How Tse2, which seems to have a cytoplasmic target4, crosses the cytoplasmic membrane of a target bacterium is not known.