Molecular sensing mechanisms of phage infection mediated through the Zorya anti-bacteriophage defense system

In the dynamic battle between bacteriophages (phages) and their bacterial hosts, sophisticated anti-phage defense systems are pivotal for bacterial survival. Among these, the recently discovered Zorya system is notable for its unique approach to phage deterrence. The Zorya type I system in Escherichia coli consists of the membrane proteins ZorAB, which are homologous to the MotAB stator units of the bacterial flagellum, and the cytoplasmic effector proteins ZorCD. In this project, we aim to elucidate the molecular mechanisms that enable the Zorya system to detect and counteract phage infections. Utilizing a combination of structure-based mutagenesis, functional assays and live-cell total-internal reflection fluorescence (TIRF) microscopy, we investigate how the Zorya system responds to phage infection. Further, we explore the activation mechanism of the Zorya system and monitor the recruitment of Zorya components to the site of infection, which is crucial for inhibiting phage replication. Our research anticipates revealing detailed insights into the molecular sensing mechanisms and interactions within the Zorya system, thus contributing significantly to our understanding of bacterial immune strategies and potentially guiding the development of novel antibacterial therapies.