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.
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.
Cell Rep. 2019 Jul 9;28(2):295-301.e4. doi: 10.1016/j.celrep.2019.06.019.
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.
许多细菌使用类似于注射器的结构（称为收缩注射系统，CIS）与靶标生物相互作用。CIS 的结构类似于无头噬菌体，并共享进化上相关的蛋白质，如尾管、鞘和基板复合物。在许多情况下，CIS 通过将效应物递送至靶细胞来介导细菌与真核生物之间的跨界相互作用。然而，特定的效应物及其作用模式通常是未知的。在这里，我们建立了一个体外模型来研究一种称为变形相关收缩结构（MACs）的细胞外 CIS（eCIS），该结构靶向真核细胞。MACs 通过易位效应物 Pne1 杀死两种真核细胞系，即秋粘虫 Sf9 细胞和 J774A.1 鼠巨噬细胞。在鉴定 Pne1 之前，尚未描述过针对真核细胞具有核酸酶活性的 CIS 效应物。我们的结果定义了一种新的 CIS 介导的细菌-真核生物相互作用机制，并且是朝着将 CIS 作为真核宿主的新型递药系统发展的一步。
