Over the past few years, numerous anti-phage defense systems have been discovered in bacteria. Although the mechanism of defense for some of these systems is understood, a major unanswered question is how these systems sense phage infection. To systematically address this question, we isolated 177 phage mutants that escape 15 different defense systems. In many cases, these escaper phages were mutated in the gene sensed by the defense system, enabling us to map the phage determinants that confer sensitivity to bacterial immunity. Our data identify specificity determinants of diverse retron systems and reveal phage-encoded triggers for multiple abortive infection systems. We find general themes in phage sensing and demonstrate that mechanistically diverse systems have converged to sense either the core replication machinery of the phage, phage structural components, or host takeover mechanisms. Combining our data with previous findings, we formulate key principles on how bacterial immune systems sense phage invaders.

在过去几年中，在细菌中发现了许多抗噬菌体防御系统。尽管了解其中一些系统的防御机制，但一个主要的未解问题是这些系统如何感知噬菌体感染。为了系统地解决这个问题，我们分离了 177 个逃避 15 种不同防御系统的噬菌体突变体。在许多情况下，这些逃逸噬菌体在防御系统检测到的基因中发生突变，使我们能够绘制出赋予细菌免疫敏感性的噬菌体决定因素。我们的数据确定了不同反转录子系统的特异性决定因素，并揭示了多种无效感染系统的噬菌体编码触发器。我们在噬菌体感应中找到了一般主题，并证明了机械上不同的系统已经融合到感应噬菌体的核心复制机制，噬菌体结构成分，或宿主接管机制。将我们的数据与之前的发现相结合，我们制定了关于细菌免疫系统如何感知噬菌体入侵者的关键原则。