Department of Biomedical Informatics and Laboratory of Systems Pharmacology, Harvard Medical School, Boston, MA, USA.
Institute of Infection, Veterinary & Ecological Sciences, University of Liverpool, Liverpool, UK; Biozentrum, University of Basel, Basel, Switzerland.
Cell Host Microbe. 2021 Nov 10;29(11):1620-1633.e8. doi: 10.1016/j.chom.2021.09.002. Epub 2021 Sep 30.
Temperate phages are pervasive in bacterial genomes, existing as vertically inherited islands termed prophages. Prophages are vulnerable to predation of their host bacterium by exogenous phages. Here, we identify BstA, a family of prophage-encoded phage-defense proteins in diverse Gram-negative bacteria. BstA localizes to sites of exogenous phage DNA replication and mediates abortive infection, suppressing the competing phage epidemic. During lytic replication, the BstA-encoding prophage is not itself inhibited by BstA due to self-immunity conferred by the anti-BstA (aba) element, a short stretch of DNA within the bstA locus. Inhibition of phage replication by distinct BstA proteins from Salmonella, Klebsiella, and Escherichia prophages is generally interchangeable, but each possesses a cognate aba element. The specificity of the aba element ensures that immunity is exclusive to the replicating prophage, preventing exploitation by variant BstA-encoding phages. The BstA protein allows prophages to defend host cells against exogenous phage attack without sacrificing the ability to replicate lytically.
温和噬菌体广泛存在于细菌基因组中，以垂直遗传的称为噬菌体的形式存在。噬菌体容易受到外源噬菌体对其宿主细菌的捕食。在这里，我们鉴定了 BstA，这是一种在多种革兰氏阴性菌中存在的噬菌体防御蛋白家族。BstA 定位于外源噬菌体 DNA 复制的部位，并介导流产感染，抑制竞争噬菌体的流行。在裂解复制过程中，由于 bstA 基因座内的短 DNA 序列 anti-BstA（aba）元件赋予的自我免疫，编码 BstA 的噬菌体不会被 BstA 自身抑制。来自沙门氏菌、克雷伯氏菌和大肠杆菌噬菌体的不同 BstA 蛋白对噬菌体复制的抑制作用通常是可互换的，但每种蛋白都有一个同源的 aba 元件。aba 元件的特异性确保了免疫是针对复制噬菌体的，从而防止了变异 BstA 编码噬菌体的利用。BstA 蛋白使噬菌体能够在不牺牲裂解复制能力的情况下，保护宿主细胞免受外源噬菌体的攻击。
