A Bacterial Phage Tail-like Structure Kills Eukaryotic Cells by Injecting a Nuclease Effector
Iara Rocchi,
Charles F. Ericson,
Kyle E. Malter,
Sahar Zargar,
Fabian Eisenstein,
Martin Pilhofer,
Sinem Beyhan,
Nicholas J. Shikuma
Affiliations
Iara Rocchi
Department of Biology, San Diego State University, San Diego, CA 92182, USA; Viral Information Institute, San Diego State University, San Diego, CA 92182, USA; Department of Infectious Diseases, J. Craig Venter Institute, La Jolla, CA 92037, USA
Charles F. Ericson
Department of Biology, San Diego State University, San Diego, CA 92182, USA; Viral Information Institute, San Diego State University, San Diego, CA 92182, USA; Institute of Molecular Biology and Biophysics, Department of Biology, ETH Zürich, Otto-Stern-Weg 5, 8093 Zürich, Switzerland
Kyle E. Malter
Department of Biology, San Diego State University, San Diego, CA 92182, USA; Viral Information Institute, San Diego State University, San Diego, CA 92182, USA
Sahar Zargar
Department of Infectious Diseases, J. Craig Venter Institute, La Jolla, CA 92037, USA
Fabian Eisenstein
Institute of Molecular Biology and Biophysics, Department of Biology, ETH Zürich, Otto-Stern-Weg 5, 8093 Zürich, Switzerland
Martin Pilhofer
Institute of Molecular Biology and Biophysics, Department of Biology, ETH Zürich, Otto-Stern-Weg 5, 8093 Zürich, Switzerland
Sinem Beyhan
Department of Biology, San Diego State University, San Diego, CA 92182, USA; Department of Infectious Diseases, J. Craig Venter Institute, La Jolla, CA 92037, USA; Corresponding author
Nicholas J. Shikuma
Department of Biology, San Diego State University, San Diego, CA 92182, USA; Viral Information Institute, San Diego State University, San Diego, CA 92182, USA; Department of Infectious Diseases, J. Craig Venter Institute, La Jolla, CA 92037, USA; Corresponding author
Summary: Many bacteria interact with target organisms using syringe-like structures called contractile injection systems (CISs). CISs structurally resemble headless bacteriophages and share evolutionarily related proteins such as the tail tube, sheath, and baseplate complex. In many cases, CISs mediate trans-kingdom interactions between bacteria and eukaryotes by delivering effectors to target cells. However, the specific effectors and their modes of action are often unknown. Here, we establish an ex vivo model to study an extracellular CIS (eCIS) called metamorphosis-associated contractile structures (MACs) that target eukaryotic cells. MACs kill two eukaryotic cell lines, fall armyworm Sf9 cells and J774A.1 murine macrophage cells, by translocating an effector termed Pne1. Before the identification of Pne1, no CIS effector exhibiting nuclease activity against eukaryotic cells had been described. Our results define a new mechanism of CIS-mediated bacteria-eukaryote interaction and are a step toward developing CISs as novel delivery systems for eukaryotic hosts. : Contractile injection systems are syringe-like structures from bacteria that often inject toxic effectors into target cells. Rocchi et al. establish an ex vivo interaction between a contractile injection system and two eukaryotic cell lines from insects and mice. Killing of target cells is dependent on an effector with nuclease activity. Keywords: phage, cell line, effector, T6SS, CIS, secretion system, MACs