Division of Biochemistry and Biotechnology, Department of Biosciences, University of Helsinki, P.O. Box 56, FI-00014, Helsinki, Finland.
Department of Bacteriology and Immunology, Medicum, Research Programs Unit, Immunobiology, University of Helsinki, P.O. Box 21, FI-00014, Helsinki, Finland.
Nat Commun. 2017 Dec 4;8(1):1915. doi: 10.1038/s41467-017-02057-3.
Eukaryotic organisms are continuously exposed to bacteriophages, which are efficient gene transfer agents in bacteria. However, bacteriophages are considered not to pass the eukaryotic cell membrane and enter nonphagocytic cells. Here we report the binding and penetration of Escherichia coli PK1A2 bacteriophage into live eukaryotic neuroblastoma cells in vitro. The phage interacts with cell surface polysialic acid, which shares structural similarity with the bacterial phage receptor. Using fluorescence and electron microscopy, we show that phages are internalized via the endolysosomal route and persist inside the human cells up to one day without affecting cell viability. Phage capsid integrity is lost in lysosomes, and the phage DNA is eventually degraded. We did not detect the entry of phage DNA into the nucleus; however, we speculate that this might occur as a rare event, and propose that this potential mechanism could explain prokaryote-eukaryote gene flow.
真核生物不断暴露于噬菌体中，噬菌体是细菌中有效的基因转移剂。然而，噬菌体被认为不能穿透真核细胞膜并进入非吞噬细胞。在这里，我们报告了大肠杆菌 PK1A2 噬菌体在体外与活真核神经母细胞瘤细胞的结合和渗透。噬菌体与细胞表面多糖结合，与细菌噬菌体受体具有结构相似性。使用荧光和电子显微镜，我们表明噬菌体通过内吞体途径被内化，并在人类细胞中持续存在长达一天而不影响细胞活力。噬菌体衣壳在溶酶体中失去完整性，噬菌体 DNA 最终被降解。我们没有检测到噬菌体 DNA 进入细胞核；然而，我们推测这可能是一个罕见的事件，并提出这种潜在的机制可以解释原核生物与真核生物的基因流动。
