Bacteria can interact with eukaryotic cells through contractile injection systems (CISs), which are evolutionarily related to the tails of bacteriophages. One type of CISs, extracellular CISs (eCISs), is released extracellularly, followed by binding to the surface of target cells and delivery of toxic effectors. Rocchi, Ericson, Malter et al. studied the interaction between an eCIS from Pseudoalteromonas luteoviolacea called metamorphosis-associated contractile structures (MACs) and insect and mammalian cells. They identified a new MAC effector, which they termed Pseudoalteromonas nuclease effector, that caused cytotoxicity in both cell types. They went on to show that killing was mediated by the nuclease activity of the bacterial effector protein. In sum, the study identifies the first CIS effector with nuclease activity that targets eukaryotic organisms.