RT Journal Article SR Electronic T1 Bacterial Phage Tail-like Structure Kills Eukaryotic Cells by Injecting a Nuclease Effector JF bioRxiv FD Cold Spring Harbor Laboratory SP 543298 DO 10.1101/543298 A1 Iara Rocchi A1 Charles Ericson A1 Kyle E. Malter A1 Sahar Zargar A1 Fabian Eisenstein A1 Martin Pilhofer A1 Sinem Beyhan A1 Nicholas J. Shikuma YR 2019 UL http://biorxiv.org/content/early/2019/02/11/543298.abstract AB Many bacteria interact with target organisms using syringe-like structures called Contractile Injection Systems (CIS). CIS structurally resemble headless bacteriophages and share evolutionarily related proteins such as the tail tube, sheath, and baseplate complex. Recent evidence shows that CIS are specialized to puncture membranes and often deliver effectors to target cells. In many cases, CIS mediate trans-kingdom interactions between bacteria and eukaryotes, however the effectors delivered to target cells and their mode of action are often unknown. In this work, we establish an in vitro model to study a CIS called Metamorphosis Associated Contractile structures (MACs) that target eukaryotic cells. We show that MACs kill two eukaryotic cell lines, Fall Armyworm Sf9 cells and J774A.1 murine macrophage cells through the action of a newly identified MAC effector, termed Pne1. To our knowledge, Pne1 is the first CIS effector exhibiting nuclease activity against eukaryotic cells. Our results define a new mechanism of CIS-mediated bacteria-eukaryote interaction and are a first step toward understanding structures with the potential to be developed as novel delivery systems for eukaryotic hosts.