Mycobacteriophages are a diverse group of viruses infecting Mycobacterium with substantial therapeutic potential. However, as this potential becomes realized, the molecular details of phage infection and mechanisms of resistance remain ill-defined. Here we use live-cell fluorescence microscopy to visualize the spatiotemporal dynamics of mycobacteriophage infection in single cells and populations, showing that infection is dependent on the host nucleoid-associated Lsr2 protein. Mycobacteriophages preferentially adsorb at Mycobacterium smegmatis sites of new cell wall synthesis and following DNA injection, Lsr2 reorganizes away from host replication foci to establish zones of phage DNA replication (ZOPR). Cells lacking Lsr2 proceed through to cell lysis when infected but fail to generate consecutive phage bursts that trigger epidemic spread of phage particles to neighbouring cells. Many mycobacteriophages code for their own Lsr2-related proteins, and although their roles are unknown, they do not rescue the loss of host Lsr2.

分枝杆菌噬菌体是感染分枝杆菌的多种病毒，具有巨大的治疗潜力。然而，随着这种潜力的实现，噬菌体感染的分子细节和耐药机制仍然不明确。在这里，我们使用活细胞荧光显微镜观察单细胞和群体中分枝杆菌噬菌体感染的时空动态，表明感染依赖于宿主核相关的 Lsr2 蛋白。分枝杆菌噬菌体优先吸附在耻垢分枝杆菌新细胞壁合成位点，注射 DNA 后，Lsr2 进行重组，远离宿主复制灶，建立噬菌体 DNA 复制区 (ZOPR)。缺乏Lsr2的细胞在感染时会进行细胞裂解，但无法产生连续的噬菌体爆发，从而触发噬菌体颗粒向邻近细胞的流行性传播。许多分枝杆菌噬菌体编码它们自己的 Lsr2 相关蛋白，尽管它们的作用尚不清楚，但它们不能挽救宿主 Lsr2 的丢失。