Living Systems Institute, University of Exeter, Exeter, UK.
College of Life and Environmental Sciences, Geoffrey Pope, University of Exeter, Exeter, UK.
Nat Commun. 2021 Nov 2;12(1):6316. doi: 10.1038/s41467-021-26610-3.
The Ff family of filamentous bacteriophages infect gram-negative bacteria, but do not cause lysis of their host cell. Instead, new virions are extruded via the phage-encoded pIV protein, which has homology with bacterial secretins. Here, we determine the structure of pIV from the f1 filamentous bacteriophage at 2.7 Å resolution by cryo-electron microscopy, the first near-atomic structure of a phage secretin. Fifteen f1 pIV subunits assemble to form a gated channel in the bacterial outer membrane, with associated soluble domains projecting into the periplasm. We model channel opening and propose a mechanism for phage egress. By single-cell microfluidics experiments, we demonstrate the potential for secretins such as pIV to be used as adjuvants to increase the uptake and efficacy of antibiotics in bacteria. Finally, we compare the f1 pIV structure to its homologues to reveal similarities and differences between phage and bacterial secretins.
丝状噬菌体 Ff 家族感染革兰氏阴性细菌，但不会导致宿主细胞裂解。相反，新的病毒粒子通过噬菌体编码的 pIV 蛋白挤出，该蛋白与细菌分泌蛋白同源。在这里，我们通过冷冻电子显微镜确定了 f1 丝状噬菌体 pIV 的结构，分辨率为 2.7Å，这是第一个接近原子结构的噬菌体分泌蛋白。十五个 f1 pIV 亚基组装形成细菌外膜中的一个门控通道，相关的可溶性结构域突入周质。我们构建了通道开放的模型，并提出了噬菌体出芽的机制。通过单细胞微流控实验，我们证明了像 pIV 这样的分泌蛋白可以作为佐剂，增加抗生素在细菌中的摄取和疗效。最后，我们将 f1 pIV 结构与其同源物进行比较，揭示了噬菌体和细菌分泌蛋白之间的相似之处和差异。
