Bacteria can interact with different hosts through syringe-like structures called Contractile Injection Systems (CISs). CIS can be divided into two types, the type six secretion systems (T6SSs) and “extracellular CIS” (eCIS), which resemble headless bacteriophages. Both CIS and eCIS share evolutionarily similar proteins such as those of the tail, sheath, and baseplate. Although CIS have only been recently studied, evidence shows that they can mediate trans-kingdom interactions between bacteria and eukaryotes. Our lab described a CIS called Metamorphosis Associated Contractile structures (MACs) that possess the ability to induce the metamorphic development of a model tubeworm. Currently, it is unclear how MACs target and interact with their eukaryotic hosts. We established an in vitro model to study MACs and their effect on eukaryotic cells and showed that MACs can cause cell death in two eukaryotic cell lines, mouse derived macrophage and insect cell lines. Furthermore, we identified a MAC effector, which contains endo-nuclease activity, that is responsible for causing cell death. Our results define a new mechanism of CIS-mediated bacteria-eukaryote interaction and is a first step toward understanding structures with the potential to be developed as novel delivery systems to eukaryotic hosts.