Rajaure Manoj, Berry Joel, Kongari Rohit, Cahill Jesse, Young Ry
Center for Phage Technology, Department of Biochemistry and Biophysics, Texas A&M University, College Station, TX 77843-2128; and.
Department of Microbiology, Pasteur Institute, 75724 Paris, France.
Proc Natl Acad Sci U S A. 2015 Apr 28;112(17):5497-502. doi: 10.1073/pnas.1420588112. Epub 2015 Apr 13.
In general, phages cause lysis of the bacterial host to effect release of the progeny virions. Until recently, it was thought that degradation of the peptidoglycan (PG) was necessary and sufficient for osmotic bursting of the cell. Recently, we have shown that in Gram-negative hosts, phage lysis also requires the disruption of the outer membrane (OM). This is accomplished by spanins, which are phage-encoded proteins that connect the cytoplasmic membrane (inner membrane, IM) and the OM. The mechanism by which the spanins destroy the OM is unknown. Here we show that the spanins of the paradigm coliphage lambda mediate efficient membrane fusion. This supports the notion that the last step of lysis is the fusion of the IM and OM. Moreover, data are provided indicating that spanin-mediated fusion is regulated by the meshwork of the PG, thus coupling fusion to murein degradation by the phage endolysin. Because endolysin function requires the formation of μm-scale holes by the phage holin, the lysis pathway is seen to require dramatic dynamics on the part of the OM and IM, as well as destruction of the PG.
一般来说，噬菌体通过使细菌宿主裂解来实现子代病毒粒子的释放。直到最近，人们还认为肽聚糖（PG）的降解对于细胞的渗透裂解是必要且充分的。最近，我们发现，在革兰氏阴性宿主中，噬菌体裂解还需要破坏外膜（OM）。这是由spanin蛋白完成的，spanin是噬菌体编码的连接细胞质膜（内膜，IM）和外膜的蛋白质。spanin破坏外膜的机制尚不清楚。在这里，我们表明典型的大肠杆菌噬菌体λ的spanin介导了有效的膜融合。这支持了裂解的最后一步是内膜和外膜融合的观点。此外，我们提供的数据表明，spanin介导的融合受PG网络的调控，从而将融合与噬菌体溶菌酶对胞壁质的降解联系起来。由于溶菌酶的功能需要噬菌体孔蛋白形成微米级的孔，因此裂解途径似乎需要外膜和内膜发生剧烈的动态变化，以及肽聚糖的破坏。
